Practice Alert

A new, 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar 13), from Wyeth Pharmaceuticals was licensed by the US Food and Drug Administration (FDA) in February for use in all children ages 6 weeks to 59 months. The new vaccine was licensed for the prevention of invasive pneumococcal disease (pneumonia, meningitis, and bacteremia) and otitis media.¹ PCV13 is meant to replace the 7-valent PCV7 (Prevnar), and will offer protection against a wider array of pneumococcal serotypes.¹

Invasive pneumococcal disease in kids has diminished substantially

Soon after PCV7 was included in the routine child immunization schedule, the incidence of invasive pneumococcal disease (IPD) began to decline.^2-5 In 1 study, the annual rate of IPD among children younger than 5 years of age decreased from 98.7 cases/100,000 in 1998–1999 to 22.6 cases/100,000 in 2006-2007.³ This decline was due to a decrease in the rate of disease caused by the 7 vaccine serotypes, from 81.9 cases/100,000 to 0.4 cases/100,000.

However, during that same time period, the rate of IPD caused by nonvaccine serotypes increased from 16.8 cases/100,000 population to 22.1 cases/100,000.³ The percentage of IPD caused by nonvaccine serotypes rose from 20% to 90% among children younger than 5 years of age during that time period.³

Fewer cases in adults, as well
In addition to the decline of IPD in children, there has also been a decline in adults. In those older than age 65, the rate of IPD decreased from 60.1/100,000 to 38.2/100,000 between 1998 and 2007—most likely because routine use of the PCV7 vaccine in children has resulted in decreased carriage and transmission of infection from children to adults.³ As in children, the decline was due to a decreasing incidence of infection from PCV7 vaccine serotypes, from 33.7 cases/100,000 to 3.3 cases/100,000. At the same time, the rate of disease caused by nonvaccine serotypes increased from 26.4 cases/100,000 to 34.9 cases/100,000.³

Nonvaccine serotypes still cause concern
While the overall decline in IPD has been a public health success, the increase in incidence of disease caused by nonvaccine serotypes has been cause for concern. According to an analysis of 2007 data from the Centers for Disease Control and Prevention (CDC)’s Active Bacterial Core surveillance, 64% of IPD cases in children younger than 5 years of age in 2006-2007 were caused by serotypes 1, 3, 5, 6A, 7F, and 19A.⁶ Several of these replacement serotypes have high levels of resistance to penicillin and erythromycin. This trend is what led to the development of the PCV13, which adds these 6 to the 7 serotypes covered by Prevnar.

The dosing schedule is complicated

The recommended schedule for the older PCV7 vaccine has always been a challenge, because the number of doses depends on the age of the child when first vaccinated.^7,8 The introduction of PCV13 adds to the complexity, because many children will be in the midst of a PCV7 series when they make the transition to PCV13.

The Advisory Committee on Immunization Practices (ACIP) recommendations on how many doses of PCV13 a child should receive depend now on the age at which the first PCV vaccine was received (either PCV7 or PCV13), the number of doses of each received, and the presence or absence of high-risk medical conditions. These recommendations are summarized below and illustrated in TABLE 1 and TABLE 2.

TABLE 1
PCV13: Routine vaccination schedule

TABLE 2
In transition: From PCV7 to PCV13

For a child who started PCV7 on time and is in mid series, the recommendation is to simply finish the series with PCV13.

If a child has completed a series of PCV7, the recommendation is to give him or her 1 dose of PCV13 up to age 59 months. (If the child has a chronic underlying medical condition, this age is extended to 71 months.¹)

Infants between the ages of 1 and 6 months who have never received any PCV product should complete a series of PCV13 at 2, 4, 6, and 12 to 15 months—the same time line as the PCV7 series.

Children ages 7 to 59 months who have not been vaccinated with PCV7 or PCV13 previously should receive 1 to 3 doses of PCV13, depending on their age at the time when vaccination begins and whether underlying medical conditions are present (TABLE 3).

Healthy children ages 24 to 59 months without previous PCV vaccine should receive 1 dose of PCV13.

Children ages 24 to 71 months without previous PCV vaccine who have a chronic medical condition that increases their risk for pneumococcal disease should receive 2 doses of PCV13, 8 weeks apart.¹

TABLE 3
Underlying conditions that place kids at risk for pneumococcal disease

Recommendations for children at higher risk

Provisional recommendations from ACIP advise that children 2 through 18 years of age at increased risk for invasive pneumococcal disease should also receive 23-valent pneumococcal polysaccharide vaccine (PPSV23). Ideally, the child should have received all of the recommended doses of PCV13 before the physician administers PPSV23, with a minimum interval of at least 8 weeks after the last dose of PCV13.

However, some children will have previously received PPSV23. They should also receive the recommended PCV13 doses. A second dose of PPSV23 is recommended 5 years after the first dose of PPSV23 for children who have sickle cell disease, or functional or anatomic asplenia, human immunodeficiency virus (HIV) infection, or other immunocompromising conditions. No more than 2 PPSV23 doses are recommended.⁹

The ACIP provisional recommendations also say that a single dose of PCV13 may be administered to children ages 6 to 18 years who are at increased risk for IPD because of sickle cell disease, HIV infection or other immunocompromising condition, cochlear implant, or cerebrospinal fluid leaks, regardless of whether they have previously received PCV7 or PPSV23.⁹ This, however, is an off-label recommendation.

The usual contraindications
PCV13 is contraindicated among individuals known to have a severe allergic reaction to any component of PCV13 or PCV7 or to any diphtheria toxoid-containing vaccine, because the pneumococcal antigens are conjugated to a diphtheria carrier protein.¹

A useful vaccine, with its share of challenges

The pneumococcal conjugate vaccine combats infections such as pneumococcal pneumonia and meningitis, which are potentially serious—even though their incidence is relatively low.

The vaccine’s high private-sector cost—reported by the manufacturer to the CDC as $435 for the full, 4-dose series of PCV13—can be a drawback for the family physician trying to keep a full array of vaccine products on hand.¹⁰ Eligible low-income and uninsured children can receive free vaccine under the federal Vaccines for Children Program, and providers who choose to enroll in the program can access free vaccines and may charge for the expense of administering them.¹¹

With this hurdle overcome, the remaining challenge for physicians will be to stay on top of the complicated dosing schedule.

A new, 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar 13), from Wyeth Pharmaceuticals was licensed by the US Food and Drug Administration (FDA) in February for use in all children ages 6 weeks to 59 months. The new vaccine was licensed for the prevention of invasive pneumococcal disease (pneumonia, meningitis, and bacteremia) and otitis media.¹ PCV13 is meant to replace the 7-valent PCV7 (Prevnar), and will offer protection against a wider array of pneumococcal serotypes.¹

Invasive pneumococcal disease in kids has diminished substantially

Soon after PCV7 was included in the routine child immunization schedule, the incidence of invasive pneumococcal disease (IPD) began to decline.^2-5 In 1 study, the annual rate of IPD among children younger than 5 years of age decreased from 98.7 cases/100,000 in 1998–1999 to 22.6 cases/100,000 in 2006-2007.³ This decline was due to a decrease in the rate of disease caused by the 7 vaccine serotypes, from 81.9 cases/100,000 to 0.4 cases/100,000.

However, during that same time period, the rate of IPD caused by nonvaccine serotypes increased from 16.8 cases/100,000 population to 22.1 cases/100,000.³ The percentage of IPD caused by nonvaccine serotypes rose from 20% to 90% among children younger than 5 years of age during that time period.³

Fewer cases in adults, as well
In addition to the decline of IPD in children, there has also been a decline in adults. In those older than age 65, the rate of IPD decreased from 60.1/100,000 to 38.2/100,000 between 1998 and 2007—most likely because routine use of the PCV7 vaccine in children has resulted in decreased carriage and transmission of infection from children to adults.³ As in children, the decline was due to a decreasing incidence of infection from PCV7 vaccine serotypes, from 33.7 cases/100,000 to 3.3 cases/100,000. At the same time, the rate of disease caused by nonvaccine serotypes increased from 26.4 cases/100,000 to 34.9 cases/100,000.³

Nonvaccine serotypes still cause concern
While the overall decline in IPD has been a public health success, the increase in incidence of disease caused by nonvaccine serotypes has been cause for concern. According to an analysis of 2007 data from the Centers for Disease Control and Prevention (CDC)’s Active Bacterial Core surveillance, 64% of IPD cases in children younger than 5 years of age in 2006-2007 were caused by serotypes 1, 3, 5, 6A, 7F, and 19A.⁶ Several of these replacement serotypes have high levels of resistance to penicillin and erythromycin. This trend is what led to the development of the PCV13, which adds these 6 to the 7 serotypes covered by Prevnar.

The dosing schedule is complicated

The recommended schedule for the older PCV7 vaccine has always been a challenge, because the number of doses depends on the age of the child when first vaccinated.^7,8 The introduction of PCV13 adds to the complexity, because many children will be in the midst of a PCV7 series when they make the transition to PCV13.

The Advisory Committee on Immunization Practices (ACIP) recommendations on how many doses of PCV13 a child should receive depend now on the age at which the first PCV vaccine was received (either PCV7 or PCV13), the number of doses of each received, and the presence or absence of high-risk medical conditions. These recommendations are summarized below and illustrated in TABLE 1 and TABLE 2.

TABLE 1
PCV13: Routine vaccination schedule

TABLE 2
In transition: From PCV7 to PCV13

For a child who started PCV7 on time and is in mid series, the recommendation is to simply finish the series with PCV13.

If a child has completed a series of PCV7, the recommendation is to give him or her 1 dose of PCV13 up to age 59 months. (If the child has a chronic underlying medical condition, this age is extended to 71 months.¹)

Infants between the ages of 1 and 6 months who have never received any PCV product should complete a series of PCV13 at 2, 4, 6, and 12 to 15 months—the same time line as the PCV7 series.

Children ages 7 to 59 months who have not been vaccinated with PCV7 or PCV13 previously should receive 1 to 3 doses of PCV13, depending on their age at the time when vaccination begins and whether underlying medical conditions are present (TABLE 3).

Healthy children ages 24 to 59 months without previous PCV vaccine should receive 1 dose of PCV13.

Children ages 24 to 71 months without previous PCV vaccine who have a chronic medical condition that increases their risk for pneumococcal disease should receive 2 doses of PCV13, 8 weeks apart.¹

TABLE 3
Underlying conditions that place kids at risk for pneumococcal disease

Recommendations for children at higher risk

Provisional recommendations from ACIP advise that children 2 through 18 years of age at increased risk for invasive pneumococcal disease should also receive 23-valent pneumococcal polysaccharide vaccine (PPSV23). Ideally, the child should have received all of the recommended doses of PCV13 before the physician administers PPSV23, with a minimum interval of at least 8 weeks after the last dose of PCV13.

However, some children will have previously received PPSV23. They should also receive the recommended PCV13 doses. A second dose of PPSV23 is recommended 5 years after the first dose of PPSV23 for children who have sickle cell disease, or functional or anatomic asplenia, human immunodeficiency virus (HIV) infection, or other immunocompromising conditions. No more than 2 PPSV23 doses are recommended.⁹

The ACIP provisional recommendations also say that a single dose of PCV13 may be administered to children ages 6 to 18 years who are at increased risk for IPD because of sickle cell disease, HIV infection or other immunocompromising condition, cochlear implant, or cerebrospinal fluid leaks, regardless of whether they have previously received PCV7 or PPSV23.⁹ This, however, is an off-label recommendation.

The usual contraindications
PCV13 is contraindicated among individuals known to have a severe allergic reaction to any component of PCV13 or PCV7 or to any diphtheria toxoid-containing vaccine, because the pneumococcal antigens are conjugated to a diphtheria carrier protein.¹

A useful vaccine, with its share of challenges

The pneumococcal conjugate vaccine combats infections such as pneumococcal pneumonia and meningitis, which are potentially serious—even though their incidence is relatively low.

The vaccine’s high private-sector cost—reported by the manufacturer to the CDC as $435 for the full, 4-dose series of PCV13—can be a drawback for the family physician trying to keep a full array of vaccine products on hand.¹⁰ Eligible low-income and uninsured children can receive free vaccine under the federal Vaccines for Children Program, and providers who choose to enroll in the program can access free vaccines and may charge for the expense of administering them.¹¹

With this hurdle overcome, the remaining challenge for physicians will be to stay on top of the complicated dosing schedule.

A new, 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar 13), from Wyeth Pharmaceuticals was licensed by the US Food and Drug Administration (FDA) in February for use in all children ages 6 weeks to 59 months. The new vaccine was licensed for the prevention of invasive pneumococcal disease (pneumonia, meningitis, and bacteremia) and otitis media.¹ PCV13 is meant to replace the 7-valent PCV7 (Prevnar), and will offer protection against a wider array of pneumococcal serotypes.¹

Invasive pneumococcal disease in kids has diminished substantially

Soon after PCV7 was included in the routine child immunization schedule, the incidence of invasive pneumococcal disease (IPD) began to decline.^2-5 In 1 study, the annual rate of IPD among children younger than 5 years of age decreased from 98.7 cases/100,000 in 1998–1999 to 22.6 cases/100,000 in 2006-2007.³ This decline was due to a decrease in the rate of disease caused by the 7 vaccine serotypes, from 81.9 cases/100,000 to 0.4 cases/100,000.

However, during that same time period, the rate of IPD caused by nonvaccine serotypes increased from 16.8 cases/100,000 population to 22.1 cases/100,000.³ The percentage of IPD caused by nonvaccine serotypes rose from 20% to 90% among children younger than 5 years of age during that time period.³

Fewer cases in adults, as well
In addition to the decline of IPD in children, there has also been a decline in adults. In those older than age 65, the rate of IPD decreased from 60.1/100,000 to 38.2/100,000 between 1998 and 2007—most likely because routine use of the PCV7 vaccine in children has resulted in decreased carriage and transmission of infection from children to adults.³ As in children, the decline was due to a decreasing incidence of infection from PCV7 vaccine serotypes, from 33.7 cases/100,000 to 3.3 cases/100,000. At the same time, the rate of disease caused by nonvaccine serotypes increased from 26.4 cases/100,000 to 34.9 cases/100,000.³

Nonvaccine serotypes still cause concern
While the overall decline in IPD has been a public health success, the increase in incidence of disease caused by nonvaccine serotypes has been cause for concern. According to an analysis of 2007 data from the Centers for Disease Control and Prevention (CDC)’s Active Bacterial Core surveillance, 64% of IPD cases in children younger than 5 years of age in 2006-2007 were caused by serotypes 1, 3, 5, 6A, 7F, and 19A.⁶ Several of these replacement serotypes have high levels of resistance to penicillin and erythromycin. This trend is what led to the development of the PCV13, which adds these 6 to the 7 serotypes covered by Prevnar.

The dosing schedule is complicated

The recommended schedule for the older PCV7 vaccine has always been a challenge, because the number of doses depends on the age of the child when first vaccinated.^7,8 The introduction of PCV13 adds to the complexity, because many children will be in the midst of a PCV7 series when they make the transition to PCV13.

The Advisory Committee on Immunization Practices (ACIP) recommendations on how many doses of PCV13 a child should receive depend now on the age at which the first PCV vaccine was received (either PCV7 or PCV13), the number of doses of each received, and the presence or absence of high-risk medical conditions. These recommendations are summarized below and illustrated in TABLE 1 and TABLE 2.

TABLE 1
PCV13: Routine vaccination schedule

TABLE 2
In transition: From PCV7 to PCV13

For a child who started PCV7 on time and is in mid series, the recommendation is to simply finish the series with PCV13.

If a child has completed a series of PCV7, the recommendation is to give him or her 1 dose of PCV13 up to age 59 months. (If the child has a chronic underlying medical condition, this age is extended to 71 months.¹)

Infants between the ages of 1 and 6 months who have never received any PCV product should complete a series of PCV13 at 2, 4, 6, and 12 to 15 months—the same time line as the PCV7 series.

Children ages 7 to 59 months who have not been vaccinated with PCV7 or PCV13 previously should receive 1 to 3 doses of PCV13, depending on their age at the time when vaccination begins and whether underlying medical conditions are present (TABLE 3).

Healthy children ages 24 to 59 months without previous PCV vaccine should receive 1 dose of PCV13.

Children ages 24 to 71 months without previous PCV vaccine who have a chronic medical condition that increases their risk for pneumococcal disease should receive 2 doses of PCV13, 8 weeks apart.¹

TABLE 3
Underlying conditions that place kids at risk for pneumococcal disease

Recommendations for children at higher risk

Provisional recommendations from ACIP advise that children 2 through 18 years of age at increased risk for invasive pneumococcal disease should also receive 23-valent pneumococcal polysaccharide vaccine (PPSV23). Ideally, the child should have received all of the recommended doses of PCV13 before the physician administers PPSV23, with a minimum interval of at least 8 weeks after the last dose of PCV13.

However, some children will have previously received PPSV23. They should also receive the recommended PCV13 doses. A second dose of PPSV23 is recommended 5 years after the first dose of PPSV23 for children who have sickle cell disease, or functional or anatomic asplenia, human immunodeficiency virus (HIV) infection, or other immunocompromising conditions. No more than 2 PPSV23 doses are recommended.⁹

The ACIP provisional recommendations also say that a single dose of PCV13 may be administered to children ages 6 to 18 years who are at increased risk for IPD because of sickle cell disease, HIV infection or other immunocompromising condition, cochlear implant, or cerebrospinal fluid leaks, regardless of whether they have previously received PCV7 or PPSV23.⁹ This, however, is an off-label recommendation.

The usual contraindications
PCV13 is contraindicated among individuals known to have a severe allergic reaction to any component of PCV13 or PCV7 or to any diphtheria toxoid-containing vaccine, because the pneumococcal antigens are conjugated to a diphtheria carrier protein.¹

A useful vaccine, with its share of challenges

The pneumococcal conjugate vaccine combats infections such as pneumococcal pneumonia and meningitis, which are potentially serious—even though their incidence is relatively low.

The vaccine’s high private-sector cost—reported by the manufacturer to the CDC as $435 for the full, 4-dose series of PCV13—can be a drawback for the family physician trying to keep a full array of vaccine products on hand.¹⁰ Eligible low-income and uninsured children can receive free vaccine under the federal Vaccines for Children Program, and providers who choose to enroll in the program can access free vaccines and may charge for the expense of administering them.¹¹

With this hurdle overcome, the remaining challenge for physicians will be to stay on top of the complicated dosing schedule.

Late in 2009, a change in the recommendations of the US Preventive Services Task Force (USPSTF) brought more public attention to this panel than it had ever experienced before. This publicity centered on revised recommendations on breast cancer screening that pointed out that mammograms benefit a few women under 50, but are also associated with some harms. The Task Force recommended that patients and physicians discuss these potential benefits and harms and make an individual decision about whether to have a mammogram.¹

Even though the criticism was loud—and harsh—from some sectors, many professional organizations, including the American Academy of Family Physicians, the American College of Physicians, and the American College of Preventive Medicine, came to the defense of the Task Force and its rigorous, evidence-based methodology.^2-4 Both the Journal of the American Medical Association and the Annals of Internal Medicine have since published a series of articles and opinions on the controversy, most of them favorable to the Task Force and its methods.^2-9

Lost in all the brouhaha were a number of other, less controversial recommendations that the Task Force made in 2009 (and early 2010). You can find them at www.ahrq.gov/clinic/uspstfix.htm. They are categorized by strength of recommendation (TABLE 1) and listed in TABLES 2 and 3. Family physicians should review the A and B recommendations and try to incorporate those into practice. At the same time, we should avoid services in the D category, as the evidence is strong that they are not effective or cause more harm than benefit. The C and I recommendations leave more discretion for physicians and patients to decide on these interventions based on personal values and risks. A C recommendation means the service can benefit some individuals, but the totality of benefit is small. An I recommendation means that evidence is insufficient to evaluate benefits vs harms.

TABLE 1
US Preventive Services Task Force recommendation categories

TABLE 2
USPSTF recommends FOR

TABLE 3
USPSTF recommends AGAINST routinely

The A and B recommendations you may have missed

The major additions to the A and B recommendations pertained to the use of aspirin to prevent cardiovascular disease, routine screening for depression in adults and adolescents, and screening for obesity in children ages 6 and older. The other recommendations in these categories were reaffirmations of previous recommendations (asking about smoking and providing smoking cessation guidance to adults and pregnant women, advising folic acid supplementation for women planning or capable of pregnancy, and screening pregnant women for syphilis and hepatitis B virus) and the more controversial recommendation for biennial rather than annual mammography for women ages 50 to 74.

The use of aspirin to prevent myocardial infarction in men ages 45 to 79 and ischemic strokes in women ages 55 to 79 was endorsed if a patient’s risk of these cardiovascular events exceeds the risk of bleeding from regular aspirin use. The Task Force recommendation statement is available athttp://www.ahrq.gov/clinic/uspstf09/aspirincvd/aspcvdrs.htmand provides links to tools for calculating the risk of a myocardial infarction (MI) and ischemic stroke, as well as 2 tables to compare the risks and benefits of aspirin therapy for prevention.

Screening adults for depression is endorsed if “staff-assisted depression care supports” are in place to assure accurate diagnosis, effective treatment, and follow-up. Such support includes the presence of clinical staff members who can assist the primary care provider with care support or coordination, case management, or mental health treatment. The definition can be accessed athttp://www.ahrq.gov/clinic/uspstf09/adultdepression/addeprrs.htm.

One example in the statement describes “a successful study designed for practices without ready access to mental health specialty care, (in which) office staff recruited, screened, and enrolled participants who screened positive for depression before a clinic visit. If the physician confirmed the depression diagnosis, the participant was scheduled for a return visit with the physician and to meet with the nurse specialist in 1 week. The nurse specialist reassessed the patient’s level of depression, discussed treatment options and preferences, and asked the participant to complete a homework assignment. Participants completed up to 8 additional sessions that followed the same pattern, either by phone or in person.”

Screening for major depressive disorder (MDD) in adolescents 12 to 18 years of age is recommended when systems are in place to ensure accurate diagnosis, psychotherapy (cognitive-behavioral or interpersonal), and follow-up. The Task Force addressed screening for MDD only—not for less severe depression. The instruments the group recommended using included the Patient Health Questionnaire for Adolescents (PHQ-A) and the Beck Depression Inventory-Primary Care Version (BDI-PC).

The recommendation for screening for obesity in children ages 6 and older reflects the difficulty in achieving long-term, sustainable weight loss in this group. Effective comprehensive weight-management programs include counseling and other interventions that target both diet and physical activity. Behavioral interventions and parental involvement are also encouraged. Moderate- to high-intensity programs include more than 25 hours of contact with the child and/or the family over a 6-month period; less than this does not result in sustained improvement.

What about the D and I categories?

Two interventions received a D recommendation: Use of aspirin for stroke prevention in women <55 years and for MI prevention in men <45 years, and teaching breast self-examination (BSE) to women. The BSE recommendation has been misinterpreted as recommending against women performing self-breast exams. The recommendation is against formalized teaching of the procedure by physicians, as this leads to increased false positives and no improvement in outcomes when compared to women performing exams on their own.

The list of interventions receiving an I recommendation include some services that are commonly offered in the belief that they are effective. The Task Force is attempting to develop methodologies to decrease the number of interventions that receive an I recommendation. Currently, about 40% of all recommendations end up in this category, and physicians and patients alike could use more guidance on them. This plethora of recommendations made with insufficient evidence reflects the “ready, shoot, aim” philosophy of American medicine. We tend to accept and adopt new interventions before they are proven effective. The I recommendations are valuable reminders that, while many interventions are in common use, we often do not know as much as we should about their benefits and harms.

Late in 2009, a change in the recommendations of the US Preventive Services Task Force (USPSTF) brought more public attention to this panel than it had ever experienced before. This publicity centered on revised recommendations on breast cancer screening that pointed out that mammograms benefit a few women under 50, but are also associated with some harms. The Task Force recommended that patients and physicians discuss these potential benefits and harms and make an individual decision about whether to have a mammogram.¹

Even though the criticism was loud—and harsh—from some sectors, many professional organizations, including the American Academy of Family Physicians, the American College of Physicians, and the American College of Preventive Medicine, came to the defense of the Task Force and its rigorous, evidence-based methodology.^2-4 Both the Journal of the American Medical Association and the Annals of Internal Medicine have since published a series of articles and opinions on the controversy, most of them favorable to the Task Force and its methods.^2-9

Lost in all the brouhaha were a number of other, less controversial recommendations that the Task Force made in 2009 (and early 2010). You can find them at www.ahrq.gov/clinic/uspstfix.htm. They are categorized by strength of recommendation (TABLE 1) and listed in TABLES 2 and 3. Family physicians should review the A and B recommendations and try to incorporate those into practice. At the same time, we should avoid services in the D category, as the evidence is strong that they are not effective or cause more harm than benefit. The C and I recommendations leave more discretion for physicians and patients to decide on these interventions based on personal values and risks. A C recommendation means the service can benefit some individuals, but the totality of benefit is small. An I recommendation means that evidence is insufficient to evaluate benefits vs harms.

TABLE 1
US Preventive Services Task Force recommendation categories

TABLE 2
USPSTF recommends FOR

TABLE 3
USPSTF recommends AGAINST routinely

The A and B recommendations you may have missed

The major additions to the A and B recommendations pertained to the use of aspirin to prevent cardiovascular disease, routine screening for depression in adults and adolescents, and screening for obesity in children ages 6 and older. The other recommendations in these categories were reaffirmations of previous recommendations (asking about smoking and providing smoking cessation guidance to adults and pregnant women, advising folic acid supplementation for women planning or capable of pregnancy, and screening pregnant women for syphilis and hepatitis B virus) and the more controversial recommendation for biennial rather than annual mammography for women ages 50 to 74.

The use of aspirin to prevent myocardial infarction in men ages 45 to 79 and ischemic strokes in women ages 55 to 79 was endorsed if a patient’s risk of these cardiovascular events exceeds the risk of bleeding from regular aspirin use. The Task Force recommendation statement is available athttp://www.ahrq.gov/clinic/uspstf09/aspirincvd/aspcvdrs.htmand provides links to tools for calculating the risk of a myocardial infarction (MI) and ischemic stroke, as well as 2 tables to compare the risks and benefits of aspirin therapy for prevention.

Screening adults for depression is endorsed if “staff-assisted depression care supports” are in place to assure accurate diagnosis, effective treatment, and follow-up. Such support includes the presence of clinical staff members who can assist the primary care provider with care support or coordination, case management, or mental health treatment. The definition can be accessed athttp://www.ahrq.gov/clinic/uspstf09/adultdepression/addeprrs.htm.

One example in the statement describes “a successful study designed for practices without ready access to mental health specialty care, (in which) office staff recruited, screened, and enrolled participants who screened positive for depression before a clinic visit. If the physician confirmed the depression diagnosis, the participant was scheduled for a return visit with the physician and to meet with the nurse specialist in 1 week. The nurse specialist reassessed the patient’s level of depression, discussed treatment options and preferences, and asked the participant to complete a homework assignment. Participants completed up to 8 additional sessions that followed the same pattern, either by phone or in person.”

Screening for major depressive disorder (MDD) in adolescents 12 to 18 years of age is recommended when systems are in place to ensure accurate diagnosis, psychotherapy (cognitive-behavioral or interpersonal), and follow-up. The Task Force addressed screening for MDD only—not for less severe depression. The instruments the group recommended using included the Patient Health Questionnaire for Adolescents (PHQ-A) and the Beck Depression Inventory-Primary Care Version (BDI-PC).

The recommendation for screening for obesity in children ages 6 and older reflects the difficulty in achieving long-term, sustainable weight loss in this group. Effective comprehensive weight-management programs include counseling and other interventions that target both diet and physical activity. Behavioral interventions and parental involvement are also encouraged. Moderate- to high-intensity programs include more than 25 hours of contact with the child and/or the family over a 6-month period; less than this does not result in sustained improvement.

What about the D and I categories?

Two interventions received a D recommendation: Use of aspirin for stroke prevention in women <55 years and for MI prevention in men <45 years, and teaching breast self-examination (BSE) to women. The BSE recommendation has been misinterpreted as recommending against women performing self-breast exams. The recommendation is against formalized teaching of the procedure by physicians, as this leads to increased false positives and no improvement in outcomes when compared to women performing exams on their own.

The list of interventions receiving an I recommendation include some services that are commonly offered in the belief that they are effective. The Task Force is attempting to develop methodologies to decrease the number of interventions that receive an I recommendation. Currently, about 40% of all recommendations end up in this category, and physicians and patients alike could use more guidance on them. This plethora of recommendations made with insufficient evidence reflects the “ready, shoot, aim” philosophy of American medicine. We tend to accept and adopt new interventions before they are proven effective. The I recommendations are valuable reminders that, while many interventions are in common use, we often do not know as much as we should about their benefits and harms.

Late in 2009, a change in the recommendations of the US Preventive Services Task Force (USPSTF) brought more public attention to this panel than it had ever experienced before. This publicity centered on revised recommendations on breast cancer screening that pointed out that mammograms benefit a few women under 50, but are also associated with some harms. The Task Force recommended that patients and physicians discuss these potential benefits and harms and make an individual decision about whether to have a mammogram.¹

Even though the criticism was loud—and harsh—from some sectors, many professional organizations, including the American Academy of Family Physicians, the American College of Physicians, and the American College of Preventive Medicine, came to the defense of the Task Force and its rigorous, evidence-based methodology.^2-4 Both the Journal of the American Medical Association and the Annals of Internal Medicine have since published a series of articles and opinions on the controversy, most of them favorable to the Task Force and its methods.^2-9

Lost in all the brouhaha were a number of other, less controversial recommendations that the Task Force made in 2009 (and early 2010). You can find them at www.ahrq.gov/clinic/uspstfix.htm. They are categorized by strength of recommendation (TABLE 1) and listed in TABLES 2 and 3. Family physicians should review the A and B recommendations and try to incorporate those into practice. At the same time, we should avoid services in the D category, as the evidence is strong that they are not effective or cause more harm than benefit. The C and I recommendations leave more discretion for physicians and patients to decide on these interventions based on personal values and risks. A C recommendation means the service can benefit some individuals, but the totality of benefit is small. An I recommendation means that evidence is insufficient to evaluate benefits vs harms.

TABLE 1
US Preventive Services Task Force recommendation categories

TABLE 2
USPSTF recommends FOR

TABLE 3
USPSTF recommends AGAINST routinely

The A and B recommendations you may have missed

The major additions to the A and B recommendations pertained to the use of aspirin to prevent cardiovascular disease, routine screening for depression in adults and adolescents, and screening for obesity in children ages 6 and older. The other recommendations in these categories were reaffirmations of previous recommendations (asking about smoking and providing smoking cessation guidance to adults and pregnant women, advising folic acid supplementation for women planning or capable of pregnancy, and screening pregnant women for syphilis and hepatitis B virus) and the more controversial recommendation for biennial rather than annual mammography for women ages 50 to 74.

The use of aspirin to prevent myocardial infarction in men ages 45 to 79 and ischemic strokes in women ages 55 to 79 was endorsed if a patient’s risk of these cardiovascular events exceeds the risk of bleeding from regular aspirin use. The Task Force recommendation statement is available athttp://www.ahrq.gov/clinic/uspstf09/aspirincvd/aspcvdrs.htmand provides links to tools for calculating the risk of a myocardial infarction (MI) and ischemic stroke, as well as 2 tables to compare the risks and benefits of aspirin therapy for prevention.

Screening adults for depression is endorsed if “staff-assisted depression care supports” are in place to assure accurate diagnosis, effective treatment, and follow-up. Such support includes the presence of clinical staff members who can assist the primary care provider with care support or coordination, case management, or mental health treatment. The definition can be accessed athttp://www.ahrq.gov/clinic/uspstf09/adultdepression/addeprrs.htm.

One example in the statement describes “a successful study designed for practices without ready access to mental health specialty care, (in which) office staff recruited, screened, and enrolled participants who screened positive for depression before a clinic visit. If the physician confirmed the depression diagnosis, the participant was scheduled for a return visit with the physician and to meet with the nurse specialist in 1 week. The nurse specialist reassessed the patient’s level of depression, discussed treatment options and preferences, and asked the participant to complete a homework assignment. Participants completed up to 8 additional sessions that followed the same pattern, either by phone or in person.”

Screening for major depressive disorder (MDD) in adolescents 12 to 18 years of age is recommended when systems are in place to ensure accurate diagnosis, psychotherapy (cognitive-behavioral or interpersonal), and follow-up. The Task Force addressed screening for MDD only—not for less severe depression. The instruments the group recommended using included the Patient Health Questionnaire for Adolescents (PHQ-A) and the Beck Depression Inventory-Primary Care Version (BDI-PC).

The recommendation for screening for obesity in children ages 6 and older reflects the difficulty in achieving long-term, sustainable weight loss in this group. Effective comprehensive weight-management programs include counseling and other interventions that target both diet and physical activity. Behavioral interventions and parental involvement are also encouraged. Moderate- to high-intensity programs include more than 25 hours of contact with the child and/or the family over a 6-month period; less than this does not result in sustained improvement.

What about the D and I categories?

Two interventions received a D recommendation: Use of aspirin for stroke prevention in women <55 years and for MI prevention in men <45 years, and teaching breast self-examination (BSE) to women. The BSE recommendation has been misinterpreted as recommending against women performing self-breast exams. The recommendation is against formalized teaching of the procedure by physicians, as this leads to increased false positives and no improvement in outcomes when compared to women performing exams on their own.

The list of interventions receiving an I recommendation include some services that are commonly offered in the belief that they are effective. The Task Force is attempting to develop methodologies to decrease the number of interventions that receive an I recommendation. Currently, about 40% of all recommendations end up in this category, and physicians and patients alike could use more guidance on them. This plethora of recommendations made with insufficient evidence reflects the “ready, shoot, aim” philosophy of American medicine. We tend to accept and adopt new interventions before they are proven effective. The I recommendations are valuable reminders that, while many interventions are in common use, we often do not know as much as we should about their benefits and harms.

The Advisory Committee on Immunization Practices (ACIP) made a number of major new recommendations last year. These new recommendations address:

• expanded use of hepatitis A virus (HAV) vaccine
• preferences for combination vaccines
• timing of poliovirus vaccine doses
• resumption of the normal Haemophilus influenzae Type b (Hib) schedule, as shortages have resolved
• the use of a new bivalent human papilloma virus (HPV2) vaccine in women and quadrivalent (HPV4) vaccine in men
• a reduced-dose schedule for rabies postexposure prophylaxis
• proof of immunity against mumps, measles, and rubella for health care workers
• recommendations for meningococcal vaccine boosters.

Adoptive families need more protection against HAV

Each year, approximately 18,000 children are adopted from foreign countries, almost all of them born in countries with high or intermediate rates of HAV, 85% of them under 5 years of age.¹ Identifying adoptees with an acute HAV infection is problematic, because in this age group, fewer than 10% of infected children manifest jaundice.¹ The Centers for Disease Control and Prevention (CDC) has recorded a small number of cases of acute HAV infection traced back to exposure to adoptees, and there is some evidence that 1% to 6% of new international adoptees have acute, and infectious, HAV.¹

In response to these data, the most recent ACIP recommendation expands indications for HAV vaccine to include anyone who will be in close personal contact—living in the same household or providing regular babysitting—with an adoptee from any country with high or intermediate endemic rates of HAV. The vaccine should be given within the first 60 days of the adoptee’s arrival in the United States.¹The first dose of the 2-dose series should be given as soon as the adoption is planned, ideally 2 or more weeks before exposure to the adoptee.

This new recommendation adds to earlier expansions of indications for HAV vaccine, which include universal use in children, use in postexposure prophylaxis, and preexposure protection for travelers.^2,3

ACIP still prefers combination vaccines, with caveats

Increasing numbers of vaccine products with multiple antigens have reduced the number of injections needed to complete the recommended childhood immunization schedule. These new products also create a situation in which parents and physicians have to choose between using the combination products or staying with component vaccines that contain fewer antigens, but necessitate a larger number of injections.

When ACIP considered this dilemma, committee members gave the general preference to combination vaccines. At the same time, the committee acknowledged that many considerations—storage, costs, number of injections, vaccine availability, vaccination status, likelihood of improved coverage, likelihood of return visits, patient preference, and the potential for adverse events—factor into the decision.⁴

MMRV is a special case. One combination product received special attention because of the potential for increased rates of febrile seizures. Combined measles, mumps, rubella, and varicella (MMRV) vaccine is currently in short supply, but when the supply improves it will provide 1 less injection to immunize against 4 childhood viral infections at each of 2 visits. However, there is good evidence that in children 1 to 2 years of age who are receiving the first dose of MMRV, there is an additional incidence of febrile seizures of 1 in every 2300 to 2600, compared with children receiving separate doses of MMR and varicella vaccines.⁵ There is no increased risk for older children or for the second dose.

ACIP considered this risk and recommends discussing the benefits and risks of MMR and varicella separately vs using the MMRV combination vaccine. The committee notes: “Use of MMR and varicella vaccines avoids [the] increased risk for fever and febrile seizures following MMRV vaccine.”⁵

IPV combination dosing is clarified

The inclusion of inactivated poliovirus (IPV) antigen into new combination vaccine products has caused some confusion over the recommended dosing schedule of polio vaccine. ACIP has now clarified that for the recommended 4-dose IPV schedule, the fourth dose should be administered after age 4 and at least 6 months after dose 3. In addition, the minimal intervals (4 weeks) in the first 6 months of life should be used only for those traveling overseas.⁶

Resume normal Hib schedule

With the licensure of a new Hib product (Hiberix, GlaxoSmithKline) for the booster dose of Hib starting at age 15 months, the supply of Hib vaccine has stabilized. Supply is now adequate to resume all 4 doses in the routine schedule and to recall all children who had their booster dose deferred. Children can be vaccinated with Hib through the age of 59 months (prior to their fifth birthday).⁷

2 HPV vaccines are now available

With the licensure of an HPV2 vaccine for use in women in the United States (Cervarix, GlaxoSmithKline), 2 HPV vaccine products are now available for use.⁸ An HPV4 vaccine (Gardasil, Merck & Co.) was licensed in 2006. The TABLE compares the composition, dosing schedules, and precaution for these 2 products. Each requires 3 doses, but the age ranges and dosing schedules are slightly different. The HPV4 vaccine contains antigens against HPV types 16 and 18, which cause 70% of cervical cancers and precancerous lesions, and types 6 and 11, which cause 90% of anogenital warts.⁹

The HPV2 vaccine contains antigens for HPV types 16 and 18 only and does not protect against warts. The bivalent product appears to produce a higher level of antibody response and may provide better cross protection against other HPV types. ACIP compared effectiveness studies of both vaccines and decided to show no preference for either vaccine for the prevention of cervical cancer and precancerous lesions.

TABLE
HPV vaccines: A side-by-side comparison

The recommendation is for routine vaccination with an HPV product for all adolescent girls ages 11 to 12, with catch-up through age 26. If a female wants protection against anogenital warts, HPV4 is recommended. It is preferable to complete a 3-dose series with the same product, but if this is not possible, a series can be completed with the other product. The HPV4 vaccine is made using yeast, and prefilled HPV2 syringes contain latex. Hypersensitivity to these substances is a contraindication to their use. Patients who receive either vaccine should be observed for 15 minutes after the injection to prevent injury from syncope.

HPV4 in men. The HPV4 vaccine has now been licensed in the United States for use in males ages 9 to 26 to prevent anogenital warts. It may also protect against HPV-caused cancers (oral, genital, and anal), but the proof of that is still lacking. ACIP debated whether to recommend HPV4 for boys routinely at age 11 to 12 and decided against this. Instead the group voted for a “permissive” recommendation that states HPV4 may be given to adolescents and young men ages 9 to 26 to prevent warts and that protection is better if it is administered before exposure.¹⁰ This allows vaccine use in young males to be provided in the Vaccines for Children Program, but falls short of including it in the routine vaccine schedules.

The reasons for not recommending HPV4 routinely in young men were the cost and the perception that anogenital warts are primarily a cosmetic problem, although it was acknowledged that they can cause serious psychological morbidity. ACIP acknowledged that using HPV4 in men might lead to more protection for women because viral spread would be reduced, but stated that much more protection for women would be gained from a higher level of vaccination among women. As the evidence of protection against HPV-related cancers in men is gathered, ACIP will probably revisit this recommendation.

For a more detailed discussion of the issues posed by these 2 vaccines, see “The case for HPV immunization” in the Journal of Family Practice, December 2009.¹¹

Rabies vaccine: 4 doses are sufficient

Due to a threatened shortage of rabies vaccine, ACIP commissioned a study to determine if a 4-dose series might be as effective as the licensed 5-dose series. The results showed that a reduced-dose series achieved equivalent antibody levels, so ACIP voted to recommend 4 doses of vaccine at days 0, 3, 7, and 14 postexposure.¹² The vaccine should be part of a 3-pronged approach to prevent rabies after an exposure, along with rabies immune globulin administration and wound cleaning.¹³ The 4-dose schedule differs from the rabies vaccine package inserts and the FDA licensure information.

Tougher immunity criteria for health care personnel

Prior to 2009, criteria for proof of immunity to measles, mumps, or rubella among health care workers included serologic testing, history of 2 vaccines after age 1, physician-diagnosed disease, or being born prior to 1957. The new criteria require laboratory confirmation of a physician diagnosis and add a footnote to the “born before 1957” criterion that states: Institutions with unvaccinated health care workers who lack laboratory evidence of immunity should consider vaccinating them with 2 doses of MMR (for measles and mumps) and 1 dose of MMR (for rubella). In an outbreak, the new standards recommend inoculating unvaccinated health care personnel who do not have serological proof of immunity with 2 doses for outbreaks of measles or mumps and 1 dose during an outbreak of rubella.^14,15

Meningococcal booster for those at high risk

ACIP now recommends quadrivalent meningococcal conjugate vaccine (MCV4) for all teens ages 11 to 18 years and for anyone 2 to 55 years of age who is at increased risk for meningococcal disease.¹⁶ MCV4 is licensed as a single dose.

Because of the high risk for meningococcal disease among certain groups of people, as well as limited data on duration of protection, ACIP now recommends that individuals previously vaccinated with either MCV4 or meningococcal polysaccharide vaccine (MPSV4) who are at prolonged increased risk be revaccinated with MCV4.

Those who were previously vaccinated at 7 years of age or older should be revaccinated 5 years after their previous meningococcal vaccine; individuals who were previously vaccinated at ages 2 to 6 years should be revaccinated 3 years after their previous meningococcal vaccine.

Individuals at prolonged risk for meningococcal disease are those with complement component deficiencies or anatomic or functional asplenia, microbiologists who routinely work with Neisseria meningitides, and travelers to countries where meningococcal disease is hyperendemic or epidemic.

College freshmen living in dormitories who were previously vaccinated with MCV4 do not need to be revaccinated. However, college freshmen living in dormitories who were vaccinated with MPSV4 ≥5 years previously should be vaccinated with MCV4.

New pneumococcal vaccine with more coverage
A new pneumococcal conjugate vaccine (PCV13) for infants and children will be licensed soon. It will replace the PCV7 vaccine now recommended routinely. ACIP will make recommendations on how to introduce PCV13 into a schedule for infants and children who are in the middle of a PCV7 series, and for catch-up vaccination for children who have completed a PCV7 series.

The new vaccine will provide added protection against an additional 6 types of pneumococcal bacteria, and will replace the older product immediately after licensure. It is unclear what will become of unused supplies of PCV7. Physicians who need to order PCV7 in this interim period before the new vaccine is licensed will be faced with difficult choices. The options include ordering only small quantities or trying to get an advance commitment from the manufacturers to take back any unused vaccine.

The Advisory Committee on Immunization Practices (ACIP) made a number of major new recommendations last year. These new recommendations address:

• expanded use of hepatitis A virus (HAV) vaccine
• preferences for combination vaccines
• timing of poliovirus vaccine doses
• resumption of the normal Haemophilus influenzae Type b (Hib) schedule, as shortages have resolved
• the use of a new bivalent human papilloma virus (HPV2) vaccine in women and quadrivalent (HPV4) vaccine in men
• a reduced-dose schedule for rabies postexposure prophylaxis
• proof of immunity against mumps, measles, and rubella for health care workers
• recommendations for meningococcal vaccine boosters.

Adoptive families need more protection against HAV

Each year, approximately 18,000 children are adopted from foreign countries, almost all of them born in countries with high or intermediate rates of HAV, 85% of them under 5 years of age.¹ Identifying adoptees with an acute HAV infection is problematic, because in this age group, fewer than 10% of infected children manifest jaundice.¹ The Centers for Disease Control and Prevention (CDC) has recorded a small number of cases of acute HAV infection traced back to exposure to adoptees, and there is some evidence that 1% to 6% of new international adoptees have acute, and infectious, HAV.¹

In response to these data, the most recent ACIP recommendation expands indications for HAV vaccine to include anyone who will be in close personal contact—living in the same household or providing regular babysitting—with an adoptee from any country with high or intermediate endemic rates of HAV. The vaccine should be given within the first 60 days of the adoptee’s arrival in the United States.¹The first dose of the 2-dose series should be given as soon as the adoption is planned, ideally 2 or more weeks before exposure to the adoptee.

This new recommendation adds to earlier expansions of indications for HAV vaccine, which include universal use in children, use in postexposure prophylaxis, and preexposure protection for travelers.^2,3

ACIP still prefers combination vaccines, with caveats

Increasing numbers of vaccine products with multiple antigens have reduced the number of injections needed to complete the recommended childhood immunization schedule. These new products also create a situation in which parents and physicians have to choose between using the combination products or staying with component vaccines that contain fewer antigens, but necessitate a larger number of injections.

When ACIP considered this dilemma, committee members gave the general preference to combination vaccines. At the same time, the committee acknowledged that many considerations—storage, costs, number of injections, vaccine availability, vaccination status, likelihood of improved coverage, likelihood of return visits, patient preference, and the potential for adverse events—factor into the decision.⁴

MMRV is a special case. One combination product received special attention because of the potential for increased rates of febrile seizures. Combined measles, mumps, rubella, and varicella (MMRV) vaccine is currently in short supply, but when the supply improves it will provide 1 less injection to immunize against 4 childhood viral infections at each of 2 visits. However, there is good evidence that in children 1 to 2 years of age who are receiving the first dose of MMRV, there is an additional incidence of febrile seizures of 1 in every 2300 to 2600, compared with children receiving separate doses of MMR and varicella vaccines.⁵ There is no increased risk for older children or for the second dose.

ACIP considered this risk and recommends discussing the benefits and risks of MMR and varicella separately vs using the MMRV combination vaccine. The committee notes: “Use of MMR and varicella vaccines avoids [the] increased risk for fever and febrile seizures following MMRV vaccine.”⁵

IPV combination dosing is clarified

The inclusion of inactivated poliovirus (IPV) antigen into new combination vaccine products has caused some confusion over the recommended dosing schedule of polio vaccine. ACIP has now clarified that for the recommended 4-dose IPV schedule, the fourth dose should be administered after age 4 and at least 6 months after dose 3. In addition, the minimal intervals (4 weeks) in the first 6 months of life should be used only for those traveling overseas.⁶

Resume normal Hib schedule

With the licensure of a new Hib product (Hiberix, GlaxoSmithKline) for the booster dose of Hib starting at age 15 months, the supply of Hib vaccine has stabilized. Supply is now adequate to resume all 4 doses in the routine schedule and to recall all children who had their booster dose deferred. Children can be vaccinated with Hib through the age of 59 months (prior to their fifth birthday).⁷

2 HPV vaccines are now available

With the licensure of an HPV2 vaccine for use in women in the United States (Cervarix, GlaxoSmithKline), 2 HPV vaccine products are now available for use.⁸ An HPV4 vaccine (Gardasil, Merck & Co.) was licensed in 2006. The TABLE compares the composition, dosing schedules, and precaution for these 2 products. Each requires 3 doses, but the age ranges and dosing schedules are slightly different. The HPV4 vaccine contains antigens against HPV types 16 and 18, which cause 70% of cervical cancers and precancerous lesions, and types 6 and 11, which cause 90% of anogenital warts.⁹

The HPV2 vaccine contains antigens for HPV types 16 and 18 only and does not protect against warts. The bivalent product appears to produce a higher level of antibody response and may provide better cross protection against other HPV types. ACIP compared effectiveness studies of both vaccines and decided to show no preference for either vaccine for the prevention of cervical cancer and precancerous lesions.

TABLE
HPV vaccines: A side-by-side comparison

The recommendation is for routine vaccination with an HPV product for all adolescent girls ages 11 to 12, with catch-up through age 26. If a female wants protection against anogenital warts, HPV4 is recommended. It is preferable to complete a 3-dose series with the same product, but if this is not possible, a series can be completed with the other product. The HPV4 vaccine is made using yeast, and prefilled HPV2 syringes contain latex. Hypersensitivity to these substances is a contraindication to their use. Patients who receive either vaccine should be observed for 15 minutes after the injection to prevent injury from syncope.

HPV4 in men. The HPV4 vaccine has now been licensed in the United States for use in males ages 9 to 26 to prevent anogenital warts. It may also protect against HPV-caused cancers (oral, genital, and anal), but the proof of that is still lacking. ACIP debated whether to recommend HPV4 for boys routinely at age 11 to 12 and decided against this. Instead the group voted for a “permissive” recommendation that states HPV4 may be given to adolescents and young men ages 9 to 26 to prevent warts and that protection is better if it is administered before exposure.¹⁰ This allows vaccine use in young males to be provided in the Vaccines for Children Program, but falls short of including it in the routine vaccine schedules.

The reasons for not recommending HPV4 routinely in young men were the cost and the perception that anogenital warts are primarily a cosmetic problem, although it was acknowledged that they can cause serious psychological morbidity. ACIP acknowledged that using HPV4 in men might lead to more protection for women because viral spread would be reduced, but stated that much more protection for women would be gained from a higher level of vaccination among women. As the evidence of protection against HPV-related cancers in men is gathered, ACIP will probably revisit this recommendation.

For a more detailed discussion of the issues posed by these 2 vaccines, see “The case for HPV immunization” in the Journal of Family Practice, December 2009.¹¹

Rabies vaccine: 4 doses are sufficient

Due to a threatened shortage of rabies vaccine, ACIP commissioned a study to determine if a 4-dose series might be as effective as the licensed 5-dose series. The results showed that a reduced-dose series achieved equivalent antibody levels, so ACIP voted to recommend 4 doses of vaccine at days 0, 3, 7, and 14 postexposure.¹² The vaccine should be part of a 3-pronged approach to prevent rabies after an exposure, along with rabies immune globulin administration and wound cleaning.¹³ The 4-dose schedule differs from the rabies vaccine package inserts and the FDA licensure information.

Tougher immunity criteria for health care personnel

Prior to 2009, criteria for proof of immunity to measles, mumps, or rubella among health care workers included serologic testing, history of 2 vaccines after age 1, physician-diagnosed disease, or being born prior to 1957. The new criteria require laboratory confirmation of a physician diagnosis and add a footnote to the “born before 1957” criterion that states: Institutions with unvaccinated health care workers who lack laboratory evidence of immunity should consider vaccinating them with 2 doses of MMR (for measles and mumps) and 1 dose of MMR (for rubella). In an outbreak, the new standards recommend inoculating unvaccinated health care personnel who do not have serological proof of immunity with 2 doses for outbreaks of measles or mumps and 1 dose during an outbreak of rubella.^14,15

Meningococcal booster for those at high risk

ACIP now recommends quadrivalent meningococcal conjugate vaccine (MCV4) for all teens ages 11 to 18 years and for anyone 2 to 55 years of age who is at increased risk for meningococcal disease.¹⁶ MCV4 is licensed as a single dose.

Because of the high risk for meningococcal disease among certain groups of people, as well as limited data on duration of protection, ACIP now recommends that individuals previously vaccinated with either MCV4 or meningococcal polysaccharide vaccine (MPSV4) who are at prolonged increased risk be revaccinated with MCV4.

Those who were previously vaccinated at 7 years of age or older should be revaccinated 5 years after their previous meningococcal vaccine; individuals who were previously vaccinated at ages 2 to 6 years should be revaccinated 3 years after their previous meningococcal vaccine.

Individuals at prolonged risk for meningococcal disease are those with complement component deficiencies or anatomic or functional asplenia, microbiologists who routinely work with Neisseria meningitides, and travelers to countries where meningococcal disease is hyperendemic or epidemic.

College freshmen living in dormitories who were previously vaccinated with MCV4 do not need to be revaccinated. However, college freshmen living in dormitories who were vaccinated with MPSV4 ≥5 years previously should be vaccinated with MCV4.

New pneumococcal vaccine with more coverage
A new pneumococcal conjugate vaccine (PCV13) for infants and children will be licensed soon. It will replace the PCV7 vaccine now recommended routinely. ACIP will make recommendations on how to introduce PCV13 into a schedule for infants and children who are in the middle of a PCV7 series, and for catch-up vaccination for children who have completed a PCV7 series.

The new vaccine will provide added protection against an additional 6 types of pneumococcal bacteria, and will replace the older product immediately after licensure. It is unclear what will become of unused supplies of PCV7. Physicians who need to order PCV7 in this interim period before the new vaccine is licensed will be faced with difficult choices. The options include ordering only small quantities or trying to get an advance commitment from the manufacturers to take back any unused vaccine.

The Advisory Committee on Immunization Practices (ACIP) made a number of major new recommendations last year. These new recommendations address:

• expanded use of hepatitis A virus (HAV) vaccine
• preferences for combination vaccines
• timing of poliovirus vaccine doses
• resumption of the normal Haemophilus influenzae Type b (Hib) schedule, as shortages have resolved
• the use of a new bivalent human papilloma virus (HPV2) vaccine in women and quadrivalent (HPV4) vaccine in men
• a reduced-dose schedule for rabies postexposure prophylaxis
• proof of immunity against mumps, measles, and rubella for health care workers
• recommendations for meningococcal vaccine boosters.

Adoptive families need more protection against HAV

Each year, approximately 18,000 children are adopted from foreign countries, almost all of them born in countries with high or intermediate rates of HAV, 85% of them under 5 years of age.¹ Identifying adoptees with an acute HAV infection is problematic, because in this age group, fewer than 10% of infected children manifest jaundice.¹ The Centers for Disease Control and Prevention (CDC) has recorded a small number of cases of acute HAV infection traced back to exposure to adoptees, and there is some evidence that 1% to 6% of new international adoptees have acute, and infectious, HAV.¹

In response to these data, the most recent ACIP recommendation expands indications for HAV vaccine to include anyone who will be in close personal contact—living in the same household or providing regular babysitting—with an adoptee from any country with high or intermediate endemic rates of HAV. The vaccine should be given within the first 60 days of the adoptee’s arrival in the United States.¹The first dose of the 2-dose series should be given as soon as the adoption is planned, ideally 2 or more weeks before exposure to the adoptee.

This new recommendation adds to earlier expansions of indications for HAV vaccine, which include universal use in children, use in postexposure prophylaxis, and preexposure protection for travelers.^2,3

ACIP still prefers combination vaccines, with caveats

Increasing numbers of vaccine products with multiple antigens have reduced the number of injections needed to complete the recommended childhood immunization schedule. These new products also create a situation in which parents and physicians have to choose between using the combination products or staying with component vaccines that contain fewer antigens, but necessitate a larger number of injections.

When ACIP considered this dilemma, committee members gave the general preference to combination vaccines. At the same time, the committee acknowledged that many considerations—storage, costs, number of injections, vaccine availability, vaccination status, likelihood of improved coverage, likelihood of return visits, patient preference, and the potential for adverse events—factor into the decision.⁴

MMRV is a special case. One combination product received special attention because of the potential for increased rates of febrile seizures. Combined measles, mumps, rubella, and varicella (MMRV) vaccine is currently in short supply, but when the supply improves it will provide 1 less injection to immunize against 4 childhood viral infections at each of 2 visits. However, there is good evidence that in children 1 to 2 years of age who are receiving the first dose of MMRV, there is an additional incidence of febrile seizures of 1 in every 2300 to 2600, compared with children receiving separate doses of MMR and varicella vaccines.⁵ There is no increased risk for older children or for the second dose.

ACIP considered this risk and recommends discussing the benefits and risks of MMR and varicella separately vs using the MMRV combination vaccine. The committee notes: “Use of MMR and varicella vaccines avoids [the] increased risk for fever and febrile seizures following MMRV vaccine.”⁵

IPV combination dosing is clarified

The inclusion of inactivated poliovirus (IPV) antigen into new combination vaccine products has caused some confusion over the recommended dosing schedule of polio vaccine. ACIP has now clarified that for the recommended 4-dose IPV schedule, the fourth dose should be administered after age 4 and at least 6 months after dose 3. In addition, the minimal intervals (4 weeks) in the first 6 months of life should be used only for those traveling overseas.⁶

Resume normal Hib schedule

With the licensure of a new Hib product (Hiberix, GlaxoSmithKline) for the booster dose of Hib starting at age 15 months, the supply of Hib vaccine has stabilized. Supply is now adequate to resume all 4 doses in the routine schedule and to recall all children who had their booster dose deferred. Children can be vaccinated with Hib through the age of 59 months (prior to their fifth birthday).⁷

2 HPV vaccines are now available

With the licensure of an HPV2 vaccine for use in women in the United States (Cervarix, GlaxoSmithKline), 2 HPV vaccine products are now available for use.⁸ An HPV4 vaccine (Gardasil, Merck & Co.) was licensed in 2006. The TABLE compares the composition, dosing schedules, and precaution for these 2 products. Each requires 3 doses, but the age ranges and dosing schedules are slightly different. The HPV4 vaccine contains antigens against HPV types 16 and 18, which cause 70% of cervical cancers and precancerous lesions, and types 6 and 11, which cause 90% of anogenital warts.⁹

The HPV2 vaccine contains antigens for HPV types 16 and 18 only and does not protect against warts. The bivalent product appears to produce a higher level of antibody response and may provide better cross protection against other HPV types. ACIP compared effectiveness studies of both vaccines and decided to show no preference for either vaccine for the prevention of cervical cancer and precancerous lesions.

TABLE
HPV vaccines: A side-by-side comparison

The recommendation is for routine vaccination with an HPV product for all adolescent girls ages 11 to 12, with catch-up through age 26. If a female wants protection against anogenital warts, HPV4 is recommended. It is preferable to complete a 3-dose series with the same product, but if this is not possible, a series can be completed with the other product. The HPV4 vaccine is made using yeast, and prefilled HPV2 syringes contain latex. Hypersensitivity to these substances is a contraindication to their use. Patients who receive either vaccine should be observed for 15 minutes after the injection to prevent injury from syncope.

HPV4 in men. The HPV4 vaccine has now been licensed in the United States for use in males ages 9 to 26 to prevent anogenital warts. It may also protect against HPV-caused cancers (oral, genital, and anal), but the proof of that is still lacking. ACIP debated whether to recommend HPV4 for boys routinely at age 11 to 12 and decided against this. Instead the group voted for a “permissive” recommendation that states HPV4 may be given to adolescents and young men ages 9 to 26 to prevent warts and that protection is better if it is administered before exposure.¹⁰ This allows vaccine use in young males to be provided in the Vaccines for Children Program, but falls short of including it in the routine vaccine schedules.

The reasons for not recommending HPV4 routinely in young men were the cost and the perception that anogenital warts are primarily a cosmetic problem, although it was acknowledged that they can cause serious psychological morbidity. ACIP acknowledged that using HPV4 in men might lead to more protection for women because viral spread would be reduced, but stated that much more protection for women would be gained from a higher level of vaccination among women. As the evidence of protection against HPV-related cancers in men is gathered, ACIP will probably revisit this recommendation.

For a more detailed discussion of the issues posed by these 2 vaccines, see “The case for HPV immunization” in the Journal of Family Practice, December 2009.¹¹

Rabies vaccine: 4 doses are sufficient

Due to a threatened shortage of rabies vaccine, ACIP commissioned a study to determine if a 4-dose series might be as effective as the licensed 5-dose series. The results showed that a reduced-dose series achieved equivalent antibody levels, so ACIP voted to recommend 4 doses of vaccine at days 0, 3, 7, and 14 postexposure.¹² The vaccine should be part of a 3-pronged approach to prevent rabies after an exposure, along with rabies immune globulin administration and wound cleaning.¹³ The 4-dose schedule differs from the rabies vaccine package inserts and the FDA licensure information.

Tougher immunity criteria for health care personnel

Prior to 2009, criteria for proof of immunity to measles, mumps, or rubella among health care workers included serologic testing, history of 2 vaccines after age 1, physician-diagnosed disease, or being born prior to 1957. The new criteria require laboratory confirmation of a physician diagnosis and add a footnote to the “born before 1957” criterion that states: Institutions with unvaccinated health care workers who lack laboratory evidence of immunity should consider vaccinating them with 2 doses of MMR (for measles and mumps) and 1 dose of MMR (for rubella). In an outbreak, the new standards recommend inoculating unvaccinated health care personnel who do not have serological proof of immunity with 2 doses for outbreaks of measles or mumps and 1 dose during an outbreak of rubella.^14,15

Meningococcal booster for those at high risk

ACIP now recommends quadrivalent meningococcal conjugate vaccine (MCV4) for all teens ages 11 to 18 years and for anyone 2 to 55 years of age who is at increased risk for meningococcal disease.¹⁶ MCV4 is licensed as a single dose.

Because of the high risk for meningococcal disease among certain groups of people, as well as limited data on duration of protection, ACIP now recommends that individuals previously vaccinated with either MCV4 or meningococcal polysaccharide vaccine (MPSV4) who are at prolonged increased risk be revaccinated with MCV4.

Those who were previously vaccinated at 7 years of age or older should be revaccinated 5 years after their previous meningococcal vaccine; individuals who were previously vaccinated at ages 2 to 6 years should be revaccinated 3 years after their previous meningococcal vaccine.

Individuals at prolonged risk for meningococcal disease are those with complement component deficiencies or anatomic or functional asplenia, microbiologists who routinely work with Neisseria meningitides, and travelers to countries where meningococcal disease is hyperendemic or epidemic.

College freshmen living in dormitories who were previously vaccinated with MCV4 do not need to be revaccinated. However, college freshmen living in dormitories who were vaccinated with MPSV4 ≥5 years previously should be vaccinated with MCV4.

New pneumococcal vaccine with more coverage
A new pneumococcal conjugate vaccine (PCV13) for infants and children will be licensed soon. It will replace the PCV7 vaccine now recommended routinely. ACIP will make recommendations on how to introduce PCV13 into a schedule for infants and children who are in the middle of a PCV7 series, and for catch-up vaccination for children who have completed a PCV7 series.

The new vaccine will provide added protection against an additional 6 types of pneumococcal bacteria, and will replace the older product immediately after licensure. It is unclear what will become of unused supplies of PCV7. Physicians who need to order PCV7 in this interim period before the new vaccine is licensed will be faced with difficult choices. The options include ordering only small quantities or trying to get an advance commitment from the manufacturers to take back any unused vaccine.

The first quadrivalent human papillomavirus vaccine (HPV4) was licensed in the United States in 2006 (Gardasil, Merck & Co., Inc.).¹ It contains viral proteins from HPV types 18, 16, 11, and 6, the types currently responsible for 70% of cervical cancers and 90% of anogenital warts.² The vaccine is licensed for use in females ages 9 to 26 years for the prevention of cervical, vulvar, and vaginal precancerous lesions and cancer, and for the prevention of anogenital warts.¹ It was recently licensed in the United States for the prevention of anogenital warts in males, as it has been in other countries.^2,3

HPV and cancer: Quantifying the threat

Human papillomavirus (HPV) is responsible for cancers at several anatomical sites, including the cervix, anus, oral mucosa, vulva, vagina, and penis.¹ The rate of cervical cancer in the United States has declined markedly since the introduction of screening programs using cervical cytology testing.¹ This decline has been predominantly in squamous cell carcinomas, not adenocarcinomas, which are located in the endocervix and harder to detect.¹

There are still around 12,000 cases of cervical cancer diagnosed each year in the United States, for an incidence of 8.1/100,000 women, and 3924 cervical cancer-related deaths.¹ In addition, 7% to 10% of the 50 million cervical cytology tests done each year require some form of follow-up. Of these, 2 million to 3 million findings requiring follow-up are atypical squamous cells of undetermined significance (ASC-US) and 1.25 million are low-grade squamous intraepithelial lesions.¹

There were more than 4000 cases of anal cancer recorded in 2003, a rate of 1.6/100,000 in women and 1.3/100,000 in men. In contrast to the trend in cervical cancer rates, anal cancer rates are increasing.⁴ It is not known how many incident cases of genital and anal warts there are annually, but some estimates place the number as high as 1 million. Lifetime cumulative risk has been estimated at 10%.⁵

Global morbidity and mortality from HPV is considerable, with 500,000 cases of cervical cancer and 260,000 cervical cancerrelated deaths reported worldwide in 2005.² Rates are highest in developing countries in Latin America, Africa, and Asia.²

The vaccine is effective in women

HPV4 has proven to be highly effective in women ages 15 to 26 who have not been previously infected with the HPV types in the vaccine. Effectiveness has been 98% to 100% after 3 to 5 years in these women, using such end points as moderate and severe cervical intraepithelial neoplasia (CIN2 and CIN3), endocervical adenocarcinoma in situ (AIS), anogenital warts, and vulvar and vaginal intraepithelial neoplasia.^1,2,6 These trials are ongoing.

Efficacy among women with current or past HPV infection is less certain. Studies of this question have included only small numbers and the confidence intervals have been large and included 0. In intention-to-treat studies, efficacy has been 39% to 46% for prevention of CIN2 or 3 and AIS caused by HPV 16 and 18, 69% for prevention of HPV 16/18-related vaginal intraepithelial neoplasia, and 68.5% for vaccine type-related warts.¹

Who should be vaccinated?

According to the June 2006 recommendations of the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC), immunization with 3 doses of HPV4 should be routine for girls between the ages of 11 and 12. Vaccination may be started in girls as young as age 9 and can also be done for females between the ages of 13 and 26.¹ The ACIP recommendations are summarized in TABLE 1.

The World Health Organization (WHO) qualifies its recommendations a bit. “Routine HPV vaccination,” notes WHO, “should be included in national immunization programs provided that:

• prevention of cervical cancer or other HPV-related diseases, or both, constitutes a public health priority,
• vaccine introduction is programmatically feasible,
• sustainable financing can be secured, and
• the cost effectiveness of vaccination strategies in the country or region are considered.”²

WHO also says the vaccine is most effective prior to HPV infection and that, based on the age of initiation of sexual activity, the target population is most likely to be females 9 to 13 years of age. WHO does not recommend vaccination in males.²

In the United States, most professional organizations, including the American Academy of Family Physicians, have adopted recommendations in line with those of ACIP. One exception is the American Cancer Society (ACS), which takes issue with ACIP’s recommendations for the 19- to 26-year age group. The ACS position is that the evidence is insufficient to recommend for or against routine use of the HPV vaccine for this age group.⁷

TABLE 1
ACIP HPV4 recommendations¹

Some doubts among parents and physicians

Recent national vaccine survey data show that only 25% of females ages 13 to 17 had received 1 or more doses of HPV4 vaccine.⁸ Young women appear to be interested in the vaccine and in possibly receiving it, but they tend to underestimate their risk of contracting HPV.^9,10 Some parents are concerned that the vaccine may encourage risk-taking behavior.¹¹ Physicians report that some parents fear the vaccine is too new to be fully evaluated and are concerned that insurance may not cover the cost of the 3-shot series.¹²

Physician attitudes toward the vaccine are generally positive. Close to 90% of family physicians and 98% of pediatricians administer the vaccine in their practices. Eighty percent strongly recommend it to 13- to 15-year-olds, and 50% recommend it to 11- to 12-year-olds.

A small minority of family physicians has misconceptions regarding the vaccine:

• 15% believe an HPV test should be ordered before vaccination
• 19% believe the vaccine should not be given to those diagnosed with HPV
• 31% believe a pregnancy test should be ordered before administering the vaccine.¹²

Safety concerns, minor and major

Clinical trials conducted by the vaccine manufacturer demonstrated slightly higher rates of some systemic adverse reactions in the vaccinated group compared with placebo groups (TABLE 2). Data on adverse reactions at the injection site also showed somewhat higher percentages in the vaccine group. These trials were not large enough to detect severe, rare adverse reactions.

The CDC and the US Food and Drug Administration (FDA) collaboratively operate a passive reporting system, the Vaccine Adverse Events Reporting System (VAERS), as a way of conducting surveillance for these rare events. The manufacturer is required to report suspected adverse events to VAERS, but providers and consumers can also report any suspected adverse events.

There are problems with VAERS. Because it is a passive system, some adverse events may not be reported. At the same time, some events reported by consumers and physicians may be coincidental occurrences not caused by the vaccine. To complicate matters further, patients often receive more than 1 vaccine at the same time, so that attributing any particular adverse reaction to a single vaccine is problematic. These imperfections in VAERS should lead to caution in interpreting reports received on any 1 vaccine.

A recent article published in the Journal of the American Medical Association (JAMA) described the reports on the HPV4 vaccine received by the VAERS for the first 2½ years after licensure.¹³ Slightly more than 23 million doses had been distributed during this time, and 12,424 adverse events were reported. The most common were syncope (1847), dizziness (1763), nausea (1170), headache (957), and injection site reactions (926). Of all these reported events, 772 reactions were classified as serious, and 32 vaccine recipients died. Investigation of the deaths revealed that the mean time from vaccine to the death was 47 days, the deaths were caused by a variety of underlying conditions, and 4 deaths remained unexplained.

The only 2 serious adverse events that appeared to occur more frequently than background rates were venous thrombotic events, at 1 per 500,000 doses, and syncope, at a rate of 8.2 per 100,000 doses. The syncopal events were concentrated among the 11- to 18-year-olds and resulted in 293 falls and 200 head injuries. The authors of the JAMA article caution about attributing any cause and effect to the venous thromboembolism findings because of the high rates of oral contraceptive use in this age group, which increases the risk of this condition. Studies are ongoing to try to sort out these issues.

TABLE 2
HPV4 systemic adverse events in females, ages 9-23 years¹

New developments: HPV4 for boys, licensing a bivalent vaccine

At its meeting in October 2009, ACIP decided to approve HPV4 for the prevention of anogenital warts in boys and young men ages 9 to 26.¹⁴ The potential benefits of using the HPV vaccine in males include reduced incidence of anogenital warts, possible reduction in HPV-related cancers, and reduced transmission of the HPV viruses in the vaccine to women and other men. The ACIP panel did not recommend routine immunization, however, leaving it up to physicians and patients to decide whether the vaccine is worthwhile. The advisory group said it would take up the question of the vaccine’s effectiveness in preventing HPV-related male cancers at future meetings.

At the same meeting, ACIP also voted to recommend Cervarix, the bivalent HPV vaccine from GlaxoSmithKline, for routine use in girls 11 and 12 years of age for the prevention of cancer and precancerous lesions.¹⁴ This vaccine contains antigens against HPV types 16 and 18 and does not provide protection against genital warts. Cervarix has been licensed in other countries and, to date, has demonstrated effectiveness comparable to that of the HPV4 against HPV 16- and 18-related outcomes.^1,2,6

The availability of 2 HPV vaccines, 1 against both warts and cervical cancer and the other against cervical cancer only, will present some challenging ethical and practical issues for ACIP, as well as for states and physicians.

Unresolved issues

Some critics of the vaccine have pointed out that neither HPV vaccine has yet been proven to prevent cervical cancer. Because the amount of time it takes HPV infection to progress to cervical cancer is, on average, 10 to 20 years, vaccine trials will need to be continued for years to establish this point. However, high-grade cervical lesions and genital warts are outcomes important to patients on their own and are associated with considerable morbidity. It is unknown how continued use of the vaccine will affect the epidemiology of HPV infection and the incidence of HPV types not affected by the vaccine.

Safety monitoring of the vaccine continues. At this time it appears that syncopal episodes occur at increased rates shortly after administration of the HPV4 vaccine, and vaccine providers are encouraged to follow ACIP recommendations of a 15-minute waiting period after the administration of the vaccine.¹³ Ongoing studies will continue to look at potential rare adverse reactions and determine if the vaccine is truly a cause of venous thromboembolic events.

The approved age range for the use of HPV4 in women for the prevention of cancer, precancerous lesions, and warts may be expanded above 26 years. The benefit among women of this age will be less than for younger women, because of the higher probability of previous exposure to HPV. ACIP will need to decide on whether the vaccine should be routinely or selectively recommended above age 26.

The first quadrivalent human papillomavirus vaccine (HPV4) was licensed in the United States in 2006 (Gardasil, Merck & Co., Inc.).¹ It contains viral proteins from HPV types 18, 16, 11, and 6, the types currently responsible for 70% of cervical cancers and 90% of anogenital warts.² The vaccine is licensed for use in females ages 9 to 26 years for the prevention of cervical, vulvar, and vaginal precancerous lesions and cancer, and for the prevention of anogenital warts.¹ It was recently licensed in the United States for the prevention of anogenital warts in males, as it has been in other countries.^2,3

HPV and cancer: Quantifying the threat

Human papillomavirus (HPV) is responsible for cancers at several anatomical sites, including the cervix, anus, oral mucosa, vulva, vagina, and penis.¹ The rate of cervical cancer in the United States has declined markedly since the introduction of screening programs using cervical cytology testing.¹ This decline has been predominantly in squamous cell carcinomas, not adenocarcinomas, which are located in the endocervix and harder to detect.¹

There are still around 12,000 cases of cervical cancer diagnosed each year in the United States, for an incidence of 8.1/100,000 women, and 3924 cervical cancer-related deaths.¹ In addition, 7% to 10% of the 50 million cervical cytology tests done each year require some form of follow-up. Of these, 2 million to 3 million findings requiring follow-up are atypical squamous cells of undetermined significance (ASC-US) and 1.25 million are low-grade squamous intraepithelial lesions.¹

There were more than 4000 cases of anal cancer recorded in 2003, a rate of 1.6/100,000 in women and 1.3/100,000 in men. In contrast to the trend in cervical cancer rates, anal cancer rates are increasing.⁴ It is not known how many incident cases of genital and anal warts there are annually, but some estimates place the number as high as 1 million. Lifetime cumulative risk has been estimated at 10%.⁵

Global morbidity and mortality from HPV is considerable, with 500,000 cases of cervical cancer and 260,000 cervical cancerrelated deaths reported worldwide in 2005.² Rates are highest in developing countries in Latin America, Africa, and Asia.²

The vaccine is effective in women

HPV4 has proven to be highly effective in women ages 15 to 26 who have not been previously infected with the HPV types in the vaccine. Effectiveness has been 98% to 100% after 3 to 5 years in these women, using such end points as moderate and severe cervical intraepithelial neoplasia (CIN2 and CIN3), endocervical adenocarcinoma in situ (AIS), anogenital warts, and vulvar and vaginal intraepithelial neoplasia.^1,2,6 These trials are ongoing.

Efficacy among women with current or past HPV infection is less certain. Studies of this question have included only small numbers and the confidence intervals have been large and included 0. In intention-to-treat studies, efficacy has been 39% to 46% for prevention of CIN2 or 3 and AIS caused by HPV 16 and 18, 69% for prevention of HPV 16/18-related vaginal intraepithelial neoplasia, and 68.5% for vaccine type-related warts.¹

Who should be vaccinated?

According to the June 2006 recommendations of the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC), immunization with 3 doses of HPV4 should be routine for girls between the ages of 11 and 12. Vaccination may be started in girls as young as age 9 and can also be done for females between the ages of 13 and 26.¹ The ACIP recommendations are summarized in TABLE 1.

The World Health Organization (WHO) qualifies its recommendations a bit. “Routine HPV vaccination,” notes WHO, “should be included in national immunization programs provided that:

• prevention of cervical cancer or other HPV-related diseases, or both, constitutes a public health priority,
• vaccine introduction is programmatically feasible,
• sustainable financing can be secured, and
• the cost effectiveness of vaccination strategies in the country or region are considered.”²

WHO also says the vaccine is most effective prior to HPV infection and that, based on the age of initiation of sexual activity, the target population is most likely to be females 9 to 13 years of age. WHO does not recommend vaccination in males.²

In the United States, most professional organizations, including the American Academy of Family Physicians, have adopted recommendations in line with those of ACIP. One exception is the American Cancer Society (ACS), which takes issue with ACIP’s recommendations for the 19- to 26-year age group. The ACS position is that the evidence is insufficient to recommend for or against routine use of the HPV vaccine for this age group.⁷

TABLE 1
ACIP HPV4 recommendations¹

Some doubts among parents and physicians

Recent national vaccine survey data show that only 25% of females ages 13 to 17 had received 1 or more doses of HPV4 vaccine.⁸ Young women appear to be interested in the vaccine and in possibly receiving it, but they tend to underestimate their risk of contracting HPV.^9,10 Some parents are concerned that the vaccine may encourage risk-taking behavior.¹¹ Physicians report that some parents fear the vaccine is too new to be fully evaluated and are concerned that insurance may not cover the cost of the 3-shot series.¹²

Physician attitudes toward the vaccine are generally positive. Close to 90% of family physicians and 98% of pediatricians administer the vaccine in their practices. Eighty percent strongly recommend it to 13- to 15-year-olds, and 50% recommend it to 11- to 12-year-olds.

A small minority of family physicians has misconceptions regarding the vaccine:

• 15% believe an HPV test should be ordered before vaccination
• 19% believe the vaccine should not be given to those diagnosed with HPV
• 31% believe a pregnancy test should be ordered before administering the vaccine.¹²

Safety concerns, minor and major

Clinical trials conducted by the vaccine manufacturer demonstrated slightly higher rates of some systemic adverse reactions in the vaccinated group compared with placebo groups (TABLE 2). Data on adverse reactions at the injection site also showed somewhat higher percentages in the vaccine group. These trials were not large enough to detect severe, rare adverse reactions.

The CDC and the US Food and Drug Administration (FDA) collaboratively operate a passive reporting system, the Vaccine Adverse Events Reporting System (VAERS), as a way of conducting surveillance for these rare events. The manufacturer is required to report suspected adverse events to VAERS, but providers and consumers can also report any suspected adverse events.

There are problems with VAERS. Because it is a passive system, some adverse events may not be reported. At the same time, some events reported by consumers and physicians may be coincidental occurrences not caused by the vaccine. To complicate matters further, patients often receive more than 1 vaccine at the same time, so that attributing any particular adverse reaction to a single vaccine is problematic. These imperfections in VAERS should lead to caution in interpreting reports received on any 1 vaccine.

A recent article published in the Journal of the American Medical Association (JAMA) described the reports on the HPV4 vaccine received by the VAERS for the first 2½ years after licensure.¹³ Slightly more than 23 million doses had been distributed during this time, and 12,424 adverse events were reported. The most common were syncope (1847), dizziness (1763), nausea (1170), headache (957), and injection site reactions (926). Of all these reported events, 772 reactions were classified as serious, and 32 vaccine recipients died. Investigation of the deaths revealed that the mean time from vaccine to the death was 47 days, the deaths were caused by a variety of underlying conditions, and 4 deaths remained unexplained.

The only 2 serious adverse events that appeared to occur more frequently than background rates were venous thrombotic events, at 1 per 500,000 doses, and syncope, at a rate of 8.2 per 100,000 doses. The syncopal events were concentrated among the 11- to 18-year-olds and resulted in 293 falls and 200 head injuries. The authors of the JAMA article caution about attributing any cause and effect to the venous thromboembolism findings because of the high rates of oral contraceptive use in this age group, which increases the risk of this condition. Studies are ongoing to try to sort out these issues.

TABLE 2
HPV4 systemic adverse events in females, ages 9-23 years¹

New developments: HPV4 for boys, licensing a bivalent vaccine

At its meeting in October 2009, ACIP decided to approve HPV4 for the prevention of anogenital warts in boys and young men ages 9 to 26.¹⁴ The potential benefits of using the HPV vaccine in males include reduced incidence of anogenital warts, possible reduction in HPV-related cancers, and reduced transmission of the HPV viruses in the vaccine to women and other men. The ACIP panel did not recommend routine immunization, however, leaving it up to physicians and patients to decide whether the vaccine is worthwhile. The advisory group said it would take up the question of the vaccine’s effectiveness in preventing HPV-related male cancers at future meetings.

At the same meeting, ACIP also voted to recommend Cervarix, the bivalent HPV vaccine from GlaxoSmithKline, for routine use in girls 11 and 12 years of age for the prevention of cancer and precancerous lesions.¹⁴ This vaccine contains antigens against HPV types 16 and 18 and does not provide protection against genital warts. Cervarix has been licensed in other countries and, to date, has demonstrated effectiveness comparable to that of the HPV4 against HPV 16- and 18-related outcomes.^1,2,6

The availability of 2 HPV vaccines, 1 against both warts and cervical cancer and the other against cervical cancer only, will present some challenging ethical and practical issues for ACIP, as well as for states and physicians.

Unresolved issues

Some critics of the vaccine have pointed out that neither HPV vaccine has yet been proven to prevent cervical cancer. Because the amount of time it takes HPV infection to progress to cervical cancer is, on average, 10 to 20 years, vaccine trials will need to be continued for years to establish this point. However, high-grade cervical lesions and genital warts are outcomes important to patients on their own and are associated with considerable morbidity. It is unknown how continued use of the vaccine will affect the epidemiology of HPV infection and the incidence of HPV types not affected by the vaccine.

Safety monitoring of the vaccine continues. At this time it appears that syncopal episodes occur at increased rates shortly after administration of the HPV4 vaccine, and vaccine providers are encouraged to follow ACIP recommendations of a 15-minute waiting period after the administration of the vaccine.¹³ Ongoing studies will continue to look at potential rare adverse reactions and determine if the vaccine is truly a cause of venous thromboembolic events.

The approved age range for the use of HPV4 in women for the prevention of cancer, precancerous lesions, and warts may be expanded above 26 years. The benefit among women of this age will be less than for younger women, because of the higher probability of previous exposure to HPV. ACIP will need to decide on whether the vaccine should be routinely or selectively recommended above age 26.

The first quadrivalent human papillomavirus vaccine (HPV4) was licensed in the United States in 2006 (Gardasil, Merck & Co., Inc.).¹ It contains viral proteins from HPV types 18, 16, 11, and 6, the types currently responsible for 70% of cervical cancers and 90% of anogenital warts.² The vaccine is licensed for use in females ages 9 to 26 years for the prevention of cervical, vulvar, and vaginal precancerous lesions and cancer, and for the prevention of anogenital warts.¹ It was recently licensed in the United States for the prevention of anogenital warts in males, as it has been in other countries.^2,3

HPV and cancer: Quantifying the threat

Human papillomavirus (HPV) is responsible for cancers at several anatomical sites, including the cervix, anus, oral mucosa, vulva, vagina, and penis.¹ The rate of cervical cancer in the United States has declined markedly since the introduction of screening programs using cervical cytology testing.¹ This decline has been predominantly in squamous cell carcinomas, not adenocarcinomas, which are located in the endocervix and harder to detect.¹

There are still around 12,000 cases of cervical cancer diagnosed each year in the United States, for an incidence of 8.1/100,000 women, and 3924 cervical cancer-related deaths.¹ In addition, 7% to 10% of the 50 million cervical cytology tests done each year require some form of follow-up. Of these, 2 million to 3 million findings requiring follow-up are atypical squamous cells of undetermined significance (ASC-US) and 1.25 million are low-grade squamous intraepithelial lesions.¹

There were more than 4000 cases of anal cancer recorded in 2003, a rate of 1.6/100,000 in women and 1.3/100,000 in men. In contrast to the trend in cervical cancer rates, anal cancer rates are increasing.⁴ It is not known how many incident cases of genital and anal warts there are annually, but some estimates place the number as high as 1 million. Lifetime cumulative risk has been estimated at 10%.⁵

Global morbidity and mortality from HPV is considerable, with 500,000 cases of cervical cancer and 260,000 cervical cancerrelated deaths reported worldwide in 2005.² Rates are highest in developing countries in Latin America, Africa, and Asia.²

The vaccine is effective in women

HPV4 has proven to be highly effective in women ages 15 to 26 who have not been previously infected with the HPV types in the vaccine. Effectiveness has been 98% to 100% after 3 to 5 years in these women, using such end points as moderate and severe cervical intraepithelial neoplasia (CIN2 and CIN3), endocervical adenocarcinoma in situ (AIS), anogenital warts, and vulvar and vaginal intraepithelial neoplasia.^1,2,6 These trials are ongoing.

Efficacy among women with current or past HPV infection is less certain. Studies of this question have included only small numbers and the confidence intervals have been large and included 0. In intention-to-treat studies, efficacy has been 39% to 46% for prevention of CIN2 or 3 and AIS caused by HPV 16 and 18, 69% for prevention of HPV 16/18-related vaginal intraepithelial neoplasia, and 68.5% for vaccine type-related warts.¹

Who should be vaccinated?

According to the June 2006 recommendations of the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC), immunization with 3 doses of HPV4 should be routine for girls between the ages of 11 and 12. Vaccination may be started in girls as young as age 9 and can also be done for females between the ages of 13 and 26.¹ The ACIP recommendations are summarized in TABLE 1.

The World Health Organization (WHO) qualifies its recommendations a bit. “Routine HPV vaccination,” notes WHO, “should be included in national immunization programs provided that:

• prevention of cervical cancer or other HPV-related diseases, or both, constitutes a public health priority,
• vaccine introduction is programmatically feasible,
• sustainable financing can be secured, and
• the cost effectiveness of vaccination strategies in the country or region are considered.”²

WHO also says the vaccine is most effective prior to HPV infection and that, based on the age of initiation of sexual activity, the target population is most likely to be females 9 to 13 years of age. WHO does not recommend vaccination in males.²

In the United States, most professional organizations, including the American Academy of Family Physicians, have adopted recommendations in line with those of ACIP. One exception is the American Cancer Society (ACS), which takes issue with ACIP’s recommendations for the 19- to 26-year age group. The ACS position is that the evidence is insufficient to recommend for or against routine use of the HPV vaccine for this age group.⁷

TABLE 1
ACIP HPV4 recommendations¹

Some doubts among parents and physicians

Recent national vaccine survey data show that only 25% of females ages 13 to 17 had received 1 or more doses of HPV4 vaccine.⁸ Young women appear to be interested in the vaccine and in possibly receiving it, but they tend to underestimate their risk of contracting HPV.^9,10 Some parents are concerned that the vaccine may encourage risk-taking behavior.¹¹ Physicians report that some parents fear the vaccine is too new to be fully evaluated and are concerned that insurance may not cover the cost of the 3-shot series.¹²

Physician attitudes toward the vaccine are generally positive. Close to 90% of family physicians and 98% of pediatricians administer the vaccine in their practices. Eighty percent strongly recommend it to 13- to 15-year-olds, and 50% recommend it to 11- to 12-year-olds.

A small minority of family physicians has misconceptions regarding the vaccine:

• 15% believe an HPV test should be ordered before vaccination
• 19% believe the vaccine should not be given to those diagnosed with HPV
• 31% believe a pregnancy test should be ordered before administering the vaccine.¹²

Safety concerns, minor and major

Clinical trials conducted by the vaccine manufacturer demonstrated slightly higher rates of some systemic adverse reactions in the vaccinated group compared with placebo groups (TABLE 2). Data on adverse reactions at the injection site also showed somewhat higher percentages in the vaccine group. These trials were not large enough to detect severe, rare adverse reactions.

The CDC and the US Food and Drug Administration (FDA) collaboratively operate a passive reporting system, the Vaccine Adverse Events Reporting System (VAERS), as a way of conducting surveillance for these rare events. The manufacturer is required to report suspected adverse events to VAERS, but providers and consumers can also report any suspected adverse events.

There are problems with VAERS. Because it is a passive system, some adverse events may not be reported. At the same time, some events reported by consumers and physicians may be coincidental occurrences not caused by the vaccine. To complicate matters further, patients often receive more than 1 vaccine at the same time, so that attributing any particular adverse reaction to a single vaccine is problematic. These imperfections in VAERS should lead to caution in interpreting reports received on any 1 vaccine.

A recent article published in the Journal of the American Medical Association (JAMA) described the reports on the HPV4 vaccine received by the VAERS for the first 2½ years after licensure.¹³ Slightly more than 23 million doses had been distributed during this time, and 12,424 adverse events were reported. The most common were syncope (1847), dizziness (1763), nausea (1170), headache (957), and injection site reactions (926). Of all these reported events, 772 reactions were classified as serious, and 32 vaccine recipients died. Investigation of the deaths revealed that the mean time from vaccine to the death was 47 days, the deaths were caused by a variety of underlying conditions, and 4 deaths remained unexplained.

The only 2 serious adverse events that appeared to occur more frequently than background rates were venous thrombotic events, at 1 per 500,000 doses, and syncope, at a rate of 8.2 per 100,000 doses. The syncopal events were concentrated among the 11- to 18-year-olds and resulted in 293 falls and 200 head injuries. The authors of the JAMA article caution about attributing any cause and effect to the venous thromboembolism findings because of the high rates of oral contraceptive use in this age group, which increases the risk of this condition. Studies are ongoing to try to sort out these issues.

TABLE 2
HPV4 systemic adverse events in females, ages 9-23 years¹

New developments: HPV4 for boys, licensing a bivalent vaccine

At its meeting in October 2009, ACIP decided to approve HPV4 for the prevention of anogenital warts in boys and young men ages 9 to 26.¹⁴ The potential benefits of using the HPV vaccine in males include reduced incidence of anogenital warts, possible reduction in HPV-related cancers, and reduced transmission of the HPV viruses in the vaccine to women and other men. The ACIP panel did not recommend routine immunization, however, leaving it up to physicians and patients to decide whether the vaccine is worthwhile. The advisory group said it would take up the question of the vaccine’s effectiveness in preventing HPV-related male cancers at future meetings.

At the same meeting, ACIP also voted to recommend Cervarix, the bivalent HPV vaccine from GlaxoSmithKline, for routine use in girls 11 and 12 years of age for the prevention of cancer and precancerous lesions.¹⁴ This vaccine contains antigens against HPV types 16 and 18 and does not provide protection against genital warts. Cervarix has been licensed in other countries and, to date, has demonstrated effectiveness comparable to that of the HPV4 against HPV 16- and 18-related outcomes.^1,2,6

The availability of 2 HPV vaccines, 1 against both warts and cervical cancer and the other against cervical cancer only, will present some challenging ethical and practical issues for ACIP, as well as for states and physicians.

Unresolved issues

Some critics of the vaccine have pointed out that neither HPV vaccine has yet been proven to prevent cervical cancer. Because the amount of time it takes HPV infection to progress to cervical cancer is, on average, 10 to 20 years, vaccine trials will need to be continued for years to establish this point. However, high-grade cervical lesions and genital warts are outcomes important to patients on their own and are associated with considerable morbidity. It is unknown how continued use of the vaccine will affect the epidemiology of HPV infection and the incidence of HPV types not affected by the vaccine.

Safety monitoring of the vaccine continues. At this time it appears that syncopal episodes occur at increased rates shortly after administration of the HPV4 vaccine, and vaccine providers are encouraged to follow ACIP recommendations of a 15-minute waiting period after the administration of the vaccine.¹³ Ongoing studies will continue to look at potential rare adverse reactions and determine if the vaccine is truly a cause of venous thromboembolic events.

The approved age range for the use of HPV4 in women for the prevention of cancer, precancerous lesions, and warts may be expanded above 26 years. The benefit among women of this age will be less than for younger women, because of the higher probability of previous exposure to HPV. ACIP will need to decide on whether the vaccine should be routinely or selectively recommended above age 26.

This coming flu season will be interesting—and confusing. As of August 6, 2009, the Centers for Disease Control and Prevention (CDC) reported 6506 hospitalized cases and 436 deaths from the pandemic H1N1 flu virus since the first US cases were reported in April 2009.¹ (Reporting on individual confirmed and probable cases has been discontinued.) On July 31, the World Health Organization reported pandemic influenza in 168 countries, with 162,380 reported cases and 1154 deaths.² At the same time the pandemic was developing, the seasonal flu of 2009—a relatively mild year—was tapering off. The pandemic influenza has continued to cause widespread disease in the United States throughout the summer, a somewhat unusual pattern for influenza.

So far, pandemic H1N1 flu is relatively benign, treatable

The pandemic virus, though highly infectious, has had a low case fatality rate up to now. Deaths have occurred predominantly in those with underlying medical conditions that put them at high risk of infection. Attack rates for those older than age 65 have been lower than expected, indicating that this age group may have some immunity based on past infection. The pandemic virus so far has been sensitive to both oseltamivir (Tamiflu) and zanamivir (Relenza). The resistance patterns of the key viruses from last flu season showed that the H1N1 seasonal virus was resistant to oseltamivir but sensitive to zanamivir and the adamantanes (rimantadine and amantadine), while the H3N2 virus that circulated last year was sensitive to oseltamivir.³

Fall flu season: Be prepared

So, what can you expect this fall? With pandemic H1N1 still causing illness and strains of seasonal virus circulating elsewhere in the world, no one knows for sure. But it is very likely that we will experience much higher rates of pandemic influenza once schools reopen and children begin to congregate. It is also likely we will have pandemic influenza circulating along with seasonal influenza viruses this fall and into 2010.

Immunize for seasonal flu, now

The 2009-2010 seasonal influenza vaccine will contain antigens from 3 strains: a nonpandemic H1N1 influenza A strain, an H3N2 influenza A strain, and an influenza B strain.⁴ These 3 antigens will be in all seasonal influenza vaccine products, whether they are the trivalent influenza vaccine given by injection or the live attenuated influenza vaccine provided as a nasal spray. The CDC is recommending immunization against seasonal influenza as soon as the vaccine is available.

The groups for whom seasonal influenza vaccine is recommended have not changed from last year. The recommendations are summarized in the TABLE.

TABLE
Who should get seasonal flu vaccine, 2009-2010?

Pandemic flu vaccine will be available in the fall

The vaccine for pandemic H1N1 is being produced, and the Department of Health and Human Services is projecting it to be available starting in mid- to late October. The supply will be limited at first, with increasing quantities produced as time progresses. The intent is to produce 600 million doses, or 2 per US resident, since 2 doses will be required.

Who should get the vaccine for pandemic H1N1? At its meeting at the end of July, the Advisory Committee on Immunization Practices (ACIP) recommended that vaccination efforts focus on 5 key populations:

• pregnant women
• people who live with, or care for, children <6 months of age
• health care and emergency services personnel
• individuals between the ages of 6 months and 24 years
• individuals 25 to 64 years of age who are at higher risk for novel H1N1 because of chronic health disorders or compromised immune systems.

In the event of initial shortages of the vaccine, the first 3 groups listed above should be given priority, along with children 6 months through 4 years of age and children 5 through 18 years who have chronic medical conditions.⁵ In the event of a vaccine surplus (due to low demand and/or faster-than-expected supply), prioritization will not apply and the vaccine should be administered to anyone requesting it who does not have a contraindication.

It is not known how the pandemic influenza vaccine will be distributed and administered. The extent of involvement by physician offices and clinics is undetermined and may vary by locale. There may be extensive use of mass immunization clinics and school clinics to administer the vaccine quickly. Administration will be complicated by the need for 2 doses for protection and a perception by the public that the pandemic virus is not a major concern.

Medical practices may be administering 2 influenza vaccines with different dose requirements: a single dose for seasonal influenza vaccine (except for children <9 years who are being vaccinated for the first time; they get 2 doses), and 2 doses for pandemic vaccine.

Antivirals protect vulnerable patients

Antiviral medications can be used for chemoprophylaxis, both to prevent infection in patients with a high-risk medical condition who are not, or cannot be, vaccinated (chemoprevention), and for post-exposure prophylaxis (PEP) for those who are at risk for complications or want to avoid illness. PEP is time limited (5 days), while chemoprevention may be needed for the duration of potential exposure during an outbreak or epidemic.

PEP should be considered for residents in an assisted living facility during an influenza outbreak, and for individuals who are at higher risk for influenza-related complications and who have had recent household or other close contact with a person with laboratory-confirmed influenza. Chemoprevention is an option with limited applicability at this time. If the pandemic virus were to become more virulent, it might be considered for health care workers until they had received 2 doses of vaccine.

Follow recommendations for antiviral treatment

Because resistance patterns differ among flu viruses, the decision on which antiviral or combination of antivirals to use depends on the predominant viruses circulating in the community and on laboratory tests from the infected patient to determine the influenza type involved. Current recommendations for seasonal influenza can be found at http://www2a.cdc.gov/han/ArchiveSys/ViewMsgV.asp?AlertNum=00279, and recommendations for pandemic influenza are at http://www.cdc.gov/h1n1flu/recommendations.htm#table1. These recommendations may change as the season progresses and viral resistance patterns are determined.

Consider antiviral treatment for those at high risk for complications from the virus. These include anyone hospitalized for influenza, children <5 years of age (especially those <2 years), adults ≥65 years of age, and individuals with the following conditions:

• chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, hematologic (including sickle cell disease), neurologic, neuromuscular, or metabolic disorders (including diabetes mellitus)
• immunosuppression, including that caused by medications or by HIV
• pregnant women
• individuals <19 years of age who are receiving long-term aspirin therapy
• residents of nursing homes and other chronic-care facilities.

The evidence for antiviral effectiveness is strongest if it is given within the first 48 hours of symptom onset, although in hospitalized patients, there is some evidence of effectiveness if started after this time.

Be diligent about infection control

Physicians and other health care workers will need to practice good infection control this flu season. This has been the topic of a previous Practice Alert.⁶ All health care workers should be fully immunized against influenza—seasonal and pandemic. In addition, each clinical practice should plan on implementing policies to prevent the spread of infection within the clinic or office. Such policies might include scheduling patients with respiratory illnesses for later in the day, separating patients with respiratory illnesses from other patients, requiring patients to cover their nose and mouth when they cough or sneeze, and providing tissues and hand sanitizers for patients and staff.

Physicians and staff will need to take measures to protect themselves from infection by frequent hand washing, avoiding work when ill, and using personal protective equipment when there is potential exposure to respiratory droplets.⁷ It will also be important to teach families to follow infection control practices at home whenever a household member has an influenza-like illness. Recommendations for home care can be found at www.cdc.gov/h1n1flu/guidance_homecare.htm/?x_cid=ccu071309_HomeCareGuidance_e.

Stay on top of the situation

As this influenza season progresses, keeping current about influenza recommendations will be crucial. The 3 issues to say on top of are:

1. Who should receive the vaccine for pandemic influenza and where will it be administered?
2. What influenza viruses are circulating in the community?
3. What is happening to antiviral resistance patterns and how are changes in these patterns affecting recommendations for treatment and chemoprophylaxis?

Web sites that will keep you up to date

• The CDC influenza Web site: http://www.cdc.gov/flu
• Your local and state public health department Web sites
• The American Academy of Family Physicians (AAFP) Web site: http://www.aafp.org/online/en/home.html.

CORRESPONDENCE
Doug Campos-Outcalt, MD, MPA, 550 E. Van Buren, Phoenix, AZ 85004; [email protected]

This coming flu season will be interesting—and confusing. As of August 6, 2009, the Centers for Disease Control and Prevention (CDC) reported 6506 hospitalized cases and 436 deaths from the pandemic H1N1 flu virus since the first US cases were reported in April 2009.¹ (Reporting on individual confirmed and probable cases has been discontinued.) On July 31, the World Health Organization reported pandemic influenza in 168 countries, with 162,380 reported cases and 1154 deaths.² At the same time the pandemic was developing, the seasonal flu of 2009—a relatively mild year—was tapering off. The pandemic influenza has continued to cause widespread disease in the United States throughout the summer, a somewhat unusual pattern for influenza.

So far, pandemic H1N1 flu is relatively benign, treatable

The pandemic virus, though highly infectious, has had a low case fatality rate up to now. Deaths have occurred predominantly in those with underlying medical conditions that put them at high risk of infection. Attack rates for those older than age 65 have been lower than expected, indicating that this age group may have some immunity based on past infection. The pandemic virus so far has been sensitive to both oseltamivir (Tamiflu) and zanamivir (Relenza). The resistance patterns of the key viruses from last flu season showed that the H1N1 seasonal virus was resistant to oseltamivir but sensitive to zanamivir and the adamantanes (rimantadine and amantadine), while the H3N2 virus that circulated last year was sensitive to oseltamivir.³

Fall flu season: Be prepared

So, what can you expect this fall? With pandemic H1N1 still causing illness and strains of seasonal virus circulating elsewhere in the world, no one knows for sure. But it is very likely that we will experience much higher rates of pandemic influenza once schools reopen and children begin to congregate. It is also likely we will have pandemic influenza circulating along with seasonal influenza viruses this fall and into 2010.

Immunize for seasonal flu, now

The 2009-2010 seasonal influenza vaccine will contain antigens from 3 strains: a nonpandemic H1N1 influenza A strain, an H3N2 influenza A strain, and an influenza B strain.⁴ These 3 antigens will be in all seasonal influenza vaccine products, whether they are the trivalent influenza vaccine given by injection or the live attenuated influenza vaccine provided as a nasal spray. The CDC is recommending immunization against seasonal influenza as soon as the vaccine is available.

The groups for whom seasonal influenza vaccine is recommended have not changed from last year. The recommendations are summarized in the TABLE.

TABLE
Who should get seasonal flu vaccine, 2009-2010?

Pandemic flu vaccine will be available in the fall

The vaccine for pandemic H1N1 is being produced, and the Department of Health and Human Services is projecting it to be available starting in mid- to late October. The supply will be limited at first, with increasing quantities produced as time progresses. The intent is to produce 600 million doses, or 2 per US resident, since 2 doses will be required.

Who should get the vaccine for pandemic H1N1? At its meeting at the end of July, the Advisory Committee on Immunization Practices (ACIP) recommended that vaccination efforts focus on 5 key populations:

• pregnant women
• people who live with, or care for, children <6 months of age
• health care and emergency services personnel
• individuals between the ages of 6 months and 24 years
• individuals 25 to 64 years of age who are at higher risk for novel H1N1 because of chronic health disorders or compromised immune systems.

In the event of initial shortages of the vaccine, the first 3 groups listed above should be given priority, along with children 6 months through 4 years of age and children 5 through 18 years who have chronic medical conditions.⁵ In the event of a vaccine surplus (due to low demand and/or faster-than-expected supply), prioritization will not apply and the vaccine should be administered to anyone requesting it who does not have a contraindication.

It is not known how the pandemic influenza vaccine will be distributed and administered. The extent of involvement by physician offices and clinics is undetermined and may vary by locale. There may be extensive use of mass immunization clinics and school clinics to administer the vaccine quickly. Administration will be complicated by the need for 2 doses for protection and a perception by the public that the pandemic virus is not a major concern.

Medical practices may be administering 2 influenza vaccines with different dose requirements: a single dose for seasonal influenza vaccine (except for children <9 years who are being vaccinated for the first time; they get 2 doses), and 2 doses for pandemic vaccine.

Antivirals protect vulnerable patients

Antiviral medications can be used for chemoprophylaxis, both to prevent infection in patients with a high-risk medical condition who are not, or cannot be, vaccinated (chemoprevention), and for post-exposure prophylaxis (PEP) for those who are at risk for complications or want to avoid illness. PEP is time limited (5 days), while chemoprevention may be needed for the duration of potential exposure during an outbreak or epidemic.

PEP should be considered for residents in an assisted living facility during an influenza outbreak, and for individuals who are at higher risk for influenza-related complications and who have had recent household or other close contact with a person with laboratory-confirmed influenza. Chemoprevention is an option with limited applicability at this time. If the pandemic virus were to become more virulent, it might be considered for health care workers until they had received 2 doses of vaccine.

Follow recommendations for antiviral treatment

Because resistance patterns differ among flu viruses, the decision on which antiviral or combination of antivirals to use depends on the predominant viruses circulating in the community and on laboratory tests from the infected patient to determine the influenza type involved. Current recommendations for seasonal influenza can be found at http://www2a.cdc.gov/han/ArchiveSys/ViewMsgV.asp?AlertNum=00279, and recommendations for pandemic influenza are at http://www.cdc.gov/h1n1flu/recommendations.htm#table1. These recommendations may change as the season progresses and viral resistance patterns are determined.

Consider antiviral treatment for those at high risk for complications from the virus. These include anyone hospitalized for influenza, children <5 years of age (especially those <2 years), adults ≥65 years of age, and individuals with the following conditions:

• chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, hematologic (including sickle cell disease), neurologic, neuromuscular, or metabolic disorders (including diabetes mellitus)
• immunosuppression, including that caused by medications or by HIV
• pregnant women
• individuals <19 years of age who are receiving long-term aspirin therapy
• residents of nursing homes and other chronic-care facilities.

The evidence for antiviral effectiveness is strongest if it is given within the first 48 hours of symptom onset, although in hospitalized patients, there is some evidence of effectiveness if started after this time.

Be diligent about infection control

Physicians and other health care workers will need to practice good infection control this flu season. This has been the topic of a previous Practice Alert.⁶ All health care workers should be fully immunized against influenza—seasonal and pandemic. In addition, each clinical practice should plan on implementing policies to prevent the spread of infection within the clinic or office. Such policies might include scheduling patients with respiratory illnesses for later in the day, separating patients with respiratory illnesses from other patients, requiring patients to cover their nose and mouth when they cough or sneeze, and providing tissues and hand sanitizers for patients and staff.

Physicians and staff will need to take measures to protect themselves from infection by frequent hand washing, avoiding work when ill, and using personal protective equipment when there is potential exposure to respiratory droplets.⁷ It will also be important to teach families to follow infection control practices at home whenever a household member has an influenza-like illness. Recommendations for home care can be found at www.cdc.gov/h1n1flu/guidance_homecare.htm/?x_cid=ccu071309_HomeCareGuidance_e.

Stay on top of the situation

As this influenza season progresses, keeping current about influenza recommendations will be crucial. The 3 issues to say on top of are:

1. Who should receive the vaccine for pandemic influenza and where will it be administered?
2. What influenza viruses are circulating in the community?
3. What is happening to antiviral resistance patterns and how are changes in these patterns affecting recommendations for treatment and chemoprophylaxis?

Web sites that will keep you up to date

• The CDC influenza Web site: http://www.cdc.gov/flu
• Your local and state public health department Web sites
• The American Academy of Family Physicians (AAFP) Web site: http://www.aafp.org/online/en/home.html.

CORRESPONDENCE
Doug Campos-Outcalt, MD, MPA, 550 E. Van Buren, Phoenix, AZ 85004; [email protected]

This coming flu season will be interesting—and confusing. As of August 6, 2009, the Centers for Disease Control and Prevention (CDC) reported 6506 hospitalized cases and 436 deaths from the pandemic H1N1 flu virus since the first US cases were reported in April 2009.¹ (Reporting on individual confirmed and probable cases has been discontinued.) On July 31, the World Health Organization reported pandemic influenza in 168 countries, with 162,380 reported cases and 1154 deaths.² At the same time the pandemic was developing, the seasonal flu of 2009—a relatively mild year—was tapering off. The pandemic influenza has continued to cause widespread disease in the United States throughout the summer, a somewhat unusual pattern for influenza.

So far, pandemic H1N1 flu is relatively benign, treatable

The pandemic virus, though highly infectious, has had a low case fatality rate up to now. Deaths have occurred predominantly in those with underlying medical conditions that put them at high risk of infection. Attack rates for those older than age 65 have been lower than expected, indicating that this age group may have some immunity based on past infection. The pandemic virus so far has been sensitive to both oseltamivir (Tamiflu) and zanamivir (Relenza). The resistance patterns of the key viruses from last flu season showed that the H1N1 seasonal virus was resistant to oseltamivir but sensitive to zanamivir and the adamantanes (rimantadine and amantadine), while the H3N2 virus that circulated last year was sensitive to oseltamivir.³

Fall flu season: Be prepared

So, what can you expect this fall? With pandemic H1N1 still causing illness and strains of seasonal virus circulating elsewhere in the world, no one knows for sure. But it is very likely that we will experience much higher rates of pandemic influenza once schools reopen and children begin to congregate. It is also likely we will have pandemic influenza circulating along with seasonal influenza viruses this fall and into 2010.

Immunize for seasonal flu, now

The 2009-2010 seasonal influenza vaccine will contain antigens from 3 strains: a nonpandemic H1N1 influenza A strain, an H3N2 influenza A strain, and an influenza B strain.⁴ These 3 antigens will be in all seasonal influenza vaccine products, whether they are the trivalent influenza vaccine given by injection or the live attenuated influenza vaccine provided as a nasal spray. The CDC is recommending immunization against seasonal influenza as soon as the vaccine is available.

The groups for whom seasonal influenza vaccine is recommended have not changed from last year. The recommendations are summarized in the TABLE.

TABLE
Who should get seasonal flu vaccine, 2009-2010?

Pandemic flu vaccine will be available in the fall

The vaccine for pandemic H1N1 is being produced, and the Department of Health and Human Services is projecting it to be available starting in mid- to late October. The supply will be limited at first, with increasing quantities produced as time progresses. The intent is to produce 600 million doses, or 2 per US resident, since 2 doses will be required.

Who should get the vaccine for pandemic H1N1? At its meeting at the end of July, the Advisory Committee on Immunization Practices (ACIP) recommended that vaccination efforts focus on 5 key populations:

• pregnant women
• people who live with, or care for, children <6 months of age
• health care and emergency services personnel
• individuals between the ages of 6 months and 24 years
• individuals 25 to 64 years of age who are at higher risk for novel H1N1 because of chronic health disorders or compromised immune systems.

In the event of initial shortages of the vaccine, the first 3 groups listed above should be given priority, along with children 6 months through 4 years of age and children 5 through 18 years who have chronic medical conditions.⁵ In the event of a vaccine surplus (due to low demand and/or faster-than-expected supply), prioritization will not apply and the vaccine should be administered to anyone requesting it who does not have a contraindication.

It is not known how the pandemic influenza vaccine will be distributed and administered. The extent of involvement by physician offices and clinics is undetermined and may vary by locale. There may be extensive use of mass immunization clinics and school clinics to administer the vaccine quickly. Administration will be complicated by the need for 2 doses for protection and a perception by the public that the pandemic virus is not a major concern.

Medical practices may be administering 2 influenza vaccines with different dose requirements: a single dose for seasonal influenza vaccine (except for children <9 years who are being vaccinated for the first time; they get 2 doses), and 2 doses for pandemic vaccine.

Antivirals protect vulnerable patients

Antiviral medications can be used for chemoprophylaxis, both to prevent infection in patients with a high-risk medical condition who are not, or cannot be, vaccinated (chemoprevention), and for post-exposure prophylaxis (PEP) for those who are at risk for complications or want to avoid illness. PEP is time limited (5 days), while chemoprevention may be needed for the duration of potential exposure during an outbreak or epidemic.

PEP should be considered for residents in an assisted living facility during an influenza outbreak, and for individuals who are at higher risk for influenza-related complications and who have had recent household or other close contact with a person with laboratory-confirmed influenza. Chemoprevention is an option with limited applicability at this time. If the pandemic virus were to become more virulent, it might be considered for health care workers until they had received 2 doses of vaccine.

Follow recommendations for antiviral treatment

Because resistance patterns differ among flu viruses, the decision on which antiviral or combination of antivirals to use depends on the predominant viruses circulating in the community and on laboratory tests from the infected patient to determine the influenza type involved. Current recommendations for seasonal influenza can be found at http://www2a.cdc.gov/han/ArchiveSys/ViewMsgV.asp?AlertNum=00279, and recommendations for pandemic influenza are at http://www.cdc.gov/h1n1flu/recommendations.htm#table1. These recommendations may change as the season progresses and viral resistance patterns are determined.

Consider antiviral treatment for those at high risk for complications from the virus. These include anyone hospitalized for influenza, children <5 years of age (especially those <2 years), adults ≥65 years of age, and individuals with the following conditions:

• chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, hematologic (including sickle cell disease), neurologic, neuromuscular, or metabolic disorders (including diabetes mellitus)
• immunosuppression, including that caused by medications or by HIV
• pregnant women
• individuals <19 years of age who are receiving long-term aspirin therapy
• residents of nursing homes and other chronic-care facilities.

The evidence for antiviral effectiveness is strongest if it is given within the first 48 hours of symptom onset, although in hospitalized patients, there is some evidence of effectiveness if started after this time.

Be diligent about infection control

Physicians and other health care workers will need to practice good infection control this flu season. This has been the topic of a previous Practice Alert.⁶ All health care workers should be fully immunized against influenza—seasonal and pandemic. In addition, each clinical practice should plan on implementing policies to prevent the spread of infection within the clinic or office. Such policies might include scheduling patients with respiratory illnesses for later in the day, separating patients with respiratory illnesses from other patients, requiring patients to cover their nose and mouth when they cough or sneeze, and providing tissues and hand sanitizers for patients and staff.

Physicians and staff will need to take measures to protect themselves from infection by frequent hand washing, avoiding work when ill, and using personal protective equipment when there is potential exposure to respiratory droplets.⁷ It will also be important to teach families to follow infection control practices at home whenever a household member has an influenza-like illness. Recommendations for home care can be found at www.cdc.gov/h1n1flu/guidance_homecare.htm/?x_cid=ccu071309_HomeCareGuidance_e.

Stay on top of the situation

As this influenza season progresses, keeping current about influenza recommendations will be crucial. The 3 issues to say on top of are:

1. Who should receive the vaccine for pandemic influenza and where will it be administered?
2. What influenza viruses are circulating in the community?
3. What is happening to antiviral resistance patterns and how are changes in these patterns affecting recommendations for treatment and chemoprophylaxis?

Web sites that will keep you up to date

• The CDC influenza Web site: http://www.cdc.gov/flu
• Your local and state public health department Web sites
• The American Academy of Family Physicians (AAFP) Web site: http://www.aafp.org/online/en/home.html.

CORRESPONDENCE
Doug Campos-Outcalt, MD, MPA, 550 E. Van Buren, Phoenix, AZ 85004; [email protected]

The past 12 months have been busy ones for the United States Preventive Services Task Force (USPSTF), which issued 34 new recommendations since our last Practice Alert on the group’s activity a year ago. Some recommendations address controversial topics, such as cholesterol screening, and several others—on topics such as prostate cancer screening and acceptable tests for detecting colorectal cancer—differ from those of such prominent groups as the American Cancer Society (ACS).

TABLE 1 provides a breakdown of the 5 categories of USPSTF recommendations (A, B, C, D, I). We’ll start with recent D recommendations (TABLE 2), services the Task Force recommends against, to emphasize that some preventive measures—even if they are widely touted—either provide no benefit or cause more harms than benefits.

TABLE 1
USPSTF recommendation categories

TABLE 2
The USPSTF recommends AGAINST

What not to do

The most notable new D recommendations advise against screening men ≥75 years of age for prostate cancer and against screening for colorectal cancer after age 85. The Task Force also recommends against routine screening for colorectal cancer after age 75, although individual patient considerations may influence your decision about this screen for patients between ages 76 and 85. Bear in mind that the benefits of early detection of colon cancer decline after age 75 because of the time lag between early intervention and benefit and because of competing causes of morbidity and mortality.¹

Cancer screening controversies. The recommendations for an age cutoff for prostate and colon cancer screening differ from those of the ACS, which lists no age cutoff for screening for either condition.² In fact, the Task Force does not recommend screening for prostate cancer at all. Its rationale is that before age 75, the evidence is insufficient to evaluate benefits and harms, and after 75 there is good evidence that screening does more harm than good. The ACS no longer recommends routine prostate cancer screening, but does say that when a patient leaves the decision to the physician, screening should be performed.

Thumbs down on these, too. The Task Force now recommends against using spirometry to screen for chronic obstructive pulmonary disease and against using aspirin for preventing stroke in women <55 years and myocardial infarction (MI) in men <45 years. (See below for a fuller discussion of aspirin as a preventive measure.) The Task Force also recommends against screening for asymptomatic bacteriuria in men and nonpregnant women.

Recommended interventions

Now for the preventive interventions the USPSTF advises you to perform. They include:

Prescribing low-dose aspirin. The most complicated positive recommendations are those for low-dose aspirin to prevent MI in men and stroke in women. Aspirin is effective in preventing these conditions, but carries the risk of major gastrointestinal (GI) bleeding and cerebral hemorrhage. For younger patients, as we’ve seen in the previous section, the Task Force finds the risks of prophylactic low-dose aspirin therapy outweigh the benefits. But for older patients (men between the ages of 45 and 79 years and women ages 55-79), aspirin is recommended when the potential benefit of reducing the incidence of MI in men and stroke in women outweigh the harms. To assist clinicians in weighing the potential benefits and harms, the USPSTF provides a link to a coronary heart disease risk calculator, as well as several tables comparing numbers of prevented heart attacks for men and strokes for women by age and risk category, as well as risks of bleeding complications.³

Screening for hypercholesterolemia. The Task Force’s recommendations for dyslipidemia screening differ markedly from those of the American Heart Association and the Final Report of the National Cholesterol Education Program (NCEP) Expert Panel, which recommend routine screening for all adults starting at age 20 with no age cutoff.⁴ The USPSTF recommends deferring screening until patients are older, except for those at increased risk of coronary heart disease. This controversy was described in a 2008 Practice Alert.⁵

Screening for diabetes. The only asymptomatic patients the Task Force recommends screening for diabetes are those with a sustained blood pressure of more than 135/80 mm Hg, treated or untreated. The American Diabetes Association (ADA) would cast a wider net, recommending that you consider screening for prediabetes or diabetes in those ≥45 years of age, particularly in those with a body mass index of ≥25 kg/m², and in overweight patients <45 years of age who have another risk factor for diabetes.⁶

Screening for colorectal cancer. The Task Force recommends screening adults starting at age 50 until age 75, using fecal occult blood testing, sigmoidoscopy, or colonoscopy. The ACS also recommends these screening modalities, but adds CT colonography and fecal DNA testing to the list of acceptable methods. The USPSTF found insufficient evidence to evaluate the benefits and harms of these newer tests and expressed concern over the high rate of incidental findings and the unknown long-term effects of radiation from CT colonography.

Screening adolescents. The Task Force is in favor of screening teenagers for major depressive disorder (MDD), as long as systems are in place to provide accurate diagnosis, therapy, and follow-up. High-intensity behavioral counseling for sexually active teens and adults at risk is also endorsed for the prevention of sexually transmitted infections. In both areas, however, the Task Force recognizes that adequately addressing these issues will require more than brief office- or clinic-based interventions.

Caring for pregnant women and newborns. According to the USPSTF, pregnant women should be screened for asymptomatic bacteriuria, advised to take a daily folic acid supplement, counseled about tobacco use, and encouraged to breastfeed. Newborns should be screened for congenital hypothyroidism, phenylketonuria, and hearing loss. These most recent A and B recommendations from the USPSTF are summarized in TABLE 3.

TABLE 3
The USPSTF recommends FOR

Not proven

When evidence is not available, some organizations are willing to issue guidelines based on expert opinion or consensus. Not so the USPSTF. When the Task Force members find current evidence is not sufficient to make a judgment, they put the intervention into Category I, for Insufficient. The new I recommendations range from aspirin to prevent MI and stroke in those ≥80 years to screening children for MDD and performing whole body skin examinations to detect early manifestations of skin cancer. The new I recommendations are listed in TABLE 4.

TABLE 4
Evidence is INSUFFICIENT to recommend for or against

What’s the take-home message?

All of these recent Task Force decisions add substantially to the full set of Task Force recommendations, which can be found at www.ahrq.gov/CLINIC/uspstfix.htm. Given the large number of level A and B recommendations from the Task Force, clinicians are faced with the dilemma of limited time to accomplish all the recommendations. It is reasonable to concentrate on the positive recommendations and avoid performing the interventions recommended against. The interventions in the “I” category are not as clear-cut and clinicians will continue to struggle with them, particularly when other professional organizations recommend them.

CORRESPONDENCE
Doug Campos-Outcalt, MD, MPA, 550 E. Van Buren, Phoenix, AZ 85004; [email protected].

The past 12 months have been busy ones for the United States Preventive Services Task Force (USPSTF), which issued 34 new recommendations since our last Practice Alert on the group’s activity a year ago. Some recommendations address controversial topics, such as cholesterol screening, and several others—on topics such as prostate cancer screening and acceptable tests for detecting colorectal cancer—differ from those of such prominent groups as the American Cancer Society (ACS).

TABLE 1 provides a breakdown of the 5 categories of USPSTF recommendations (A, B, C, D, I). We’ll start with recent D recommendations (TABLE 2), services the Task Force recommends against, to emphasize that some preventive measures—even if they are widely touted—either provide no benefit or cause more harms than benefits.

TABLE 1
USPSTF recommendation categories

TABLE 2
The USPSTF recommends AGAINST

What not to do

The most notable new D recommendations advise against screening men ≥75 years of age for prostate cancer and against screening for colorectal cancer after age 85. The Task Force also recommends against routine screening for colorectal cancer after age 75, although individual patient considerations may influence your decision about this screen for patients between ages 76 and 85. Bear in mind that the benefits of early detection of colon cancer decline after age 75 because of the time lag between early intervention and benefit and because of competing causes of morbidity and mortality.¹

Cancer screening controversies. The recommendations for an age cutoff for prostate and colon cancer screening differ from those of the ACS, which lists no age cutoff for screening for either condition.² In fact, the Task Force does not recommend screening for prostate cancer at all. Its rationale is that before age 75, the evidence is insufficient to evaluate benefits and harms, and after 75 there is good evidence that screening does more harm than good. The ACS no longer recommends routine prostate cancer screening, but does say that when a patient leaves the decision to the physician, screening should be performed.

Thumbs down on these, too. The Task Force now recommends against using spirometry to screen for chronic obstructive pulmonary disease and against using aspirin for preventing stroke in women <55 years and myocardial infarction (MI) in men <45 years. (See below for a fuller discussion of aspirin as a preventive measure.) The Task Force also recommends against screening for asymptomatic bacteriuria in men and nonpregnant women.

Recommended interventions

Now for the preventive interventions the USPSTF advises you to perform. They include:

Prescribing low-dose aspirin. The most complicated positive recommendations are those for low-dose aspirin to prevent MI in men and stroke in women. Aspirin is effective in preventing these conditions, but carries the risk of major gastrointestinal (GI) bleeding and cerebral hemorrhage. For younger patients, as we’ve seen in the previous section, the Task Force finds the risks of prophylactic low-dose aspirin therapy outweigh the benefits. But for older patients (men between the ages of 45 and 79 years and women ages 55-79), aspirin is recommended when the potential benefit of reducing the incidence of MI in men and stroke in women outweigh the harms. To assist clinicians in weighing the potential benefits and harms, the USPSTF provides a link to a coronary heart disease risk calculator, as well as several tables comparing numbers of prevented heart attacks for men and strokes for women by age and risk category, as well as risks of bleeding complications.³

Screening for hypercholesterolemia. The Task Force’s recommendations for dyslipidemia screening differ markedly from those of the American Heart Association and the Final Report of the National Cholesterol Education Program (NCEP) Expert Panel, which recommend routine screening for all adults starting at age 20 with no age cutoff.⁴ The USPSTF recommends deferring screening until patients are older, except for those at increased risk of coronary heart disease. This controversy was described in a 2008 Practice Alert.⁵

Screening for diabetes. The only asymptomatic patients the Task Force recommends screening for diabetes are those with a sustained blood pressure of more than 135/80 mm Hg, treated or untreated. The American Diabetes Association (ADA) would cast a wider net, recommending that you consider screening for prediabetes or diabetes in those ≥45 years of age, particularly in those with a body mass index of ≥25 kg/m², and in overweight patients <45 years of age who have another risk factor for diabetes.⁶

Screening for colorectal cancer. The Task Force recommends screening adults starting at age 50 until age 75, using fecal occult blood testing, sigmoidoscopy, or colonoscopy. The ACS also recommends these screening modalities, but adds CT colonography and fecal DNA testing to the list of acceptable methods. The USPSTF found insufficient evidence to evaluate the benefits and harms of these newer tests and expressed concern over the high rate of incidental findings and the unknown long-term effects of radiation from CT colonography.

Screening adolescents. The Task Force is in favor of screening teenagers for major depressive disorder (MDD), as long as systems are in place to provide accurate diagnosis, therapy, and follow-up. High-intensity behavioral counseling for sexually active teens and adults at risk is also endorsed for the prevention of sexually transmitted infections. In both areas, however, the Task Force recognizes that adequately addressing these issues will require more than brief office- or clinic-based interventions.

Caring for pregnant women and newborns. According to the USPSTF, pregnant women should be screened for asymptomatic bacteriuria, advised to take a daily folic acid supplement, counseled about tobacco use, and encouraged to breastfeed. Newborns should be screened for congenital hypothyroidism, phenylketonuria, and hearing loss. These most recent A and B recommendations from the USPSTF are summarized in TABLE 3.

TABLE 3
The USPSTF recommends FOR

Not proven

When evidence is not available, some organizations are willing to issue guidelines based on expert opinion or consensus. Not so the USPSTF. When the Task Force members find current evidence is not sufficient to make a judgment, they put the intervention into Category I, for Insufficient. The new I recommendations range from aspirin to prevent MI and stroke in those ≥80 years to screening children for MDD and performing whole body skin examinations to detect early manifestations of skin cancer. The new I recommendations are listed in TABLE 4.

TABLE 4
Evidence is INSUFFICIENT to recommend for or against

What’s the take-home message?

All of these recent Task Force decisions add substantially to the full set of Task Force recommendations, which can be found at www.ahrq.gov/CLINIC/uspstfix.htm. Given the large number of level A and B recommendations from the Task Force, clinicians are faced with the dilemma of limited time to accomplish all the recommendations. It is reasonable to concentrate on the positive recommendations and avoid performing the interventions recommended against. The interventions in the “I” category are not as clear-cut and clinicians will continue to struggle with them, particularly when other professional organizations recommend them.

CORRESPONDENCE
Doug Campos-Outcalt, MD, MPA, 550 E. Van Buren, Phoenix, AZ 85004; [email protected].

The past 12 months have been busy ones for the United States Preventive Services Task Force (USPSTF), which issued 34 new recommendations since our last Practice Alert on the group’s activity a year ago. Some recommendations address controversial topics, such as cholesterol screening, and several others—on topics such as prostate cancer screening and acceptable tests for detecting colorectal cancer—differ from those of such prominent groups as the American Cancer Society (ACS).

TABLE 1 provides a breakdown of the 5 categories of USPSTF recommendations (A, B, C, D, I). We’ll start with recent D recommendations (TABLE 2), services the Task Force recommends against, to emphasize that some preventive measures—even if they are widely touted—either provide no benefit or cause more harms than benefits.

TABLE 1
USPSTF recommendation categories

TABLE 2
The USPSTF recommends AGAINST

What not to do

The most notable new D recommendations advise against screening men ≥75 years of age for prostate cancer and against screening for colorectal cancer after age 85. The Task Force also recommends against routine screening for colorectal cancer after age 75, although individual patient considerations may influence your decision about this screen for patients between ages 76 and 85. Bear in mind that the benefits of early detection of colon cancer decline after age 75 because of the time lag between early intervention and benefit and because of competing causes of morbidity and mortality.¹

Cancer screening controversies. The recommendations for an age cutoff for prostate and colon cancer screening differ from those of the ACS, which lists no age cutoff for screening for either condition.² In fact, the Task Force does not recommend screening for prostate cancer at all. Its rationale is that before age 75, the evidence is insufficient to evaluate benefits and harms, and after 75 there is good evidence that screening does more harm than good. The ACS no longer recommends routine prostate cancer screening, but does say that when a patient leaves the decision to the physician, screening should be performed.

Thumbs down on these, too. The Task Force now recommends against using spirometry to screen for chronic obstructive pulmonary disease and against using aspirin for preventing stroke in women <55 years and myocardial infarction (MI) in men <45 years. (See below for a fuller discussion of aspirin as a preventive measure.) The Task Force also recommends against screening for asymptomatic bacteriuria in men and nonpregnant women.

Recommended interventions

Now for the preventive interventions the USPSTF advises you to perform. They include:

Prescribing low-dose aspirin. The most complicated positive recommendations are those for low-dose aspirin to prevent MI in men and stroke in women. Aspirin is effective in preventing these conditions, but carries the risk of major gastrointestinal (GI) bleeding and cerebral hemorrhage. For younger patients, as we’ve seen in the previous section, the Task Force finds the risks of prophylactic low-dose aspirin therapy outweigh the benefits. But for older patients (men between the ages of 45 and 79 years and women ages 55-79), aspirin is recommended when the potential benefit of reducing the incidence of MI in men and stroke in women outweigh the harms. To assist clinicians in weighing the potential benefits and harms, the USPSTF provides a link to a coronary heart disease risk calculator, as well as several tables comparing numbers of prevented heart attacks for men and strokes for women by age and risk category, as well as risks of bleeding complications.³

Screening for hypercholesterolemia. The Task Force’s recommendations for dyslipidemia screening differ markedly from those of the American Heart Association and the Final Report of the National Cholesterol Education Program (NCEP) Expert Panel, which recommend routine screening for all adults starting at age 20 with no age cutoff.⁴ The USPSTF recommends deferring screening until patients are older, except for those at increased risk of coronary heart disease. This controversy was described in a 2008 Practice Alert.⁵

Screening for diabetes. The only asymptomatic patients the Task Force recommends screening for diabetes are those with a sustained blood pressure of more than 135/80 mm Hg, treated or untreated. The American Diabetes Association (ADA) would cast a wider net, recommending that you consider screening for prediabetes or diabetes in those ≥45 years of age, particularly in those with a body mass index of ≥25 kg/m², and in overweight patients <45 years of age who have another risk factor for diabetes.⁶

Screening for colorectal cancer. The Task Force recommends screening adults starting at age 50 until age 75, using fecal occult blood testing, sigmoidoscopy, or colonoscopy. The ACS also recommends these screening modalities, but adds CT colonography and fecal DNA testing to the list of acceptable methods. The USPSTF found insufficient evidence to evaluate the benefits and harms of these newer tests and expressed concern over the high rate of incidental findings and the unknown long-term effects of radiation from CT colonography.

Screening adolescents. The Task Force is in favor of screening teenagers for major depressive disorder (MDD), as long as systems are in place to provide accurate diagnosis, therapy, and follow-up. High-intensity behavioral counseling for sexually active teens and adults at risk is also endorsed for the prevention of sexually transmitted infections. In both areas, however, the Task Force recognizes that adequately addressing these issues will require more than brief office- or clinic-based interventions.

Caring for pregnant women and newborns. According to the USPSTF, pregnant women should be screened for asymptomatic bacteriuria, advised to take a daily folic acid supplement, counseled about tobacco use, and encouraged to breastfeed. Newborns should be screened for congenital hypothyroidism, phenylketonuria, and hearing loss. These most recent A and B recommendations from the USPSTF are summarized in TABLE 3.

TABLE 3
The USPSTF recommends FOR

Not proven

When evidence is not available, some organizations are willing to issue guidelines based on expert opinion or consensus. Not so the USPSTF. When the Task Force members find current evidence is not sufficient to make a judgment, they put the intervention into Category I, for Insufficient. The new I recommendations range from aspirin to prevent MI and stroke in those ≥80 years to screening children for MDD and performing whole body skin examinations to detect early manifestations of skin cancer. The new I recommendations are listed in TABLE 4.

TABLE 4
Evidence is INSUFFICIENT to recommend for or against

What’s the take-home message?

All of these recent Task Force decisions add substantially to the full set of Task Force recommendations, which can be found at www.ahrq.gov/CLINIC/uspstfix.htm. Given the large number of level A and B recommendations from the Task Force, clinicians are faced with the dilemma of limited time to accomplish all the recommendations. It is reasonable to concentrate on the positive recommendations and avoid performing the interventions recommended against. The interventions in the “I” category are not as clear-cut and clinicians will continue to struggle with them, particularly when other professional organizations recommend them.

CORRESPONDENCE
Doug Campos-Outcalt, MD, MPA, 550 E. Van Buren, Phoenix, AZ 85004; [email protected].

Highlights of the 2008 recommendations of the CDC’s Advisory Committee on Immunization Practices (ACIP), detailed in the child and adult immunization schedules in the MMWR in January,^1,2 include:

• an expansion of the age groups for whom an annual influenza vaccine is recommended;
• expanded indications for the pneumococcal polysaccharide vaccine;
• 2 new combination vaccines for children; and
• a second rotavirus vaccine, with revised recommendations to accommodate both vaccine products.

School-age children should get flu vaccine

Children and adolescents ages 5 through 18 years are now among those who should receive an annual flu vaccine. Previously, routine vaccination was recommended only for adults and children ages 6 months through 59 months.³

Because of the timing of vaccine purchase, ACIP recognizes that routine vaccination of 5- to 18-year-olds may not be possible in some settings until next year. Family physicians who are unable to fully incorporate this new recommendation in the 2008-2009 flu season should immunize children and adolescents who are at high risk for complications of the flu. Included in that group are 5- to 18-year-olds who are on long-term aspirin therapy; have a chronic pulmonary disease, including asthma, or a cardiovascular, renal, hepatic, hematologic, or metabolic disorder; are immunosuppressed; or have a neurological or musculoskeletal disorder that alters respiratory function or the clearance of respiratory secretions. Children and adolescents who live with others at elevated risk—kids younger than 5 years, adults older than 50 years, or individuals with medical conditions that place them at high risk for severe influenza complications—should also be vaccinated.

Pneumococcal vaccine: New indications, clarifications

Two new groups have been added to the list of people for whom the 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended: asthma patients and smokers. Smoking poses as great a risk for pneumococcal pneumonia as diabetes and other chronic illnesses that had already been noted as indications for the vaccine. The number needed to vaccinate to prevent 1 case of pneumonia in smokers is 10,000 for those between the ages of 18 to 44 years, and 4000 for those ages 45 to 64 years.

A second dose. Also in 2008, ACIP clarified its dosing recommendations for PPV23: A second dose, given 5 years after the first, is recommended for those with immune suppression, sickle cell disease, or asplenia. Individuals who are 65 years of age or older should receive a second dose if they were vaccinated 5 or more years ago and were younger than 65 at the time of primary vaccination.

Not for all Native Americans. The recommendation for the use of PPV23 among the Native American population has changed, too.

Research showing high rates of invasive pneumococcal disease in Native American communities has been performed in only a few locations and cannot be generalized to all Native Americans. Therefore, ACIP has gone from recommending routine use of the vaccine among all Native Americans to a recommendation based on the same risks and age recommendations as the general population and, in communities with high rates of disease, on public health recommendations based on the incidence and epidemiology of disease.

Combination products may mean fewer injections

Two new combination vaccine products—Pentacel⁴ and Kinrix⁵—were approved last year. Both can reduce the number of injections required to complete the child immunization recommendations.

Pentacel combines 5 vaccines—diphtheria, tetanus, and pertussis (DTaP), inactivated poliovirus (IPV), and Haemophilus influenzae type b (Hib)—and is licensed for children 6 weeks through 4 years of age. Pentacel has a 4-dose schedule, with vaccine administration at 2, 4, 6, and 15 to 18 months of age. Technically, this 4-dose schedule would fulfill requirements for 4 doses of IPV. However, this could conflict with a state school immunization schedule that requires the last dose of IPV vaccine to be administered when the child is between the ages of 4 and 6 years.⁶

TABLE
Rotavirus vaccines: An administration guide

Kinrix contains DTaP and IPV. The vaccine is indicated for use as the fifth dose of DTaP and the fourth dose of IPV in children 4 through 6 years of age, following a primary series using Infanrix (DTaP) and Pediarix (DTaP, hepatitis B, and IPV).

Rotavirus vaccines: Now there are 2

There are now 2 licensed rotavirus vaccines: RotaTeq was approved in 2006,⁷ and Rotarix in 2008.⁸ ACIP does not express a preference for either product, but has revised its recommendations for rotavirus vaccination to accommodate the new release. Both RotaTeq and Rotarix are live oral vaccines, but they differ in composition and schedule of administration. Rotarix should not be given to infants who are allergic to latex, as its oral applicator contains latex rubber.

Dosing requirements. RotaTeq is administered in a 3-dose series at ages 2, 4, and 6 months; Rotarix is given in a 2-dose series at 2 and 4 months of age (TABLE). The first dose of either vaccine should be administered to children between the ages of 6 weeks and 14 weeks, 6 days. (Previously, 12 weeks was the maximum age for the first dose of rotavirus vaccine.) Neither vaccine series should be initiated in infants who are 15 weeks of age or older. The minimum interval between doses is 4 weeks, and the final dose should be administered by the age of 8 months.

It is best to complete the vaccine series with the same product. If the vaccine used initially is not available, the series can be completed with the other product, but the different number of doses required must be considered. If any dose in the series was RotaTeq or you are unable to determine which rotavirus vaccine was administered previously, a total of 3 doses should be given.

HPV and meningococcal vaccine clarification

Human papilloma virus vaccine. The HPV vaccine is recommended for all females ages 11 through 26 years, but ACIP has indicated that girls as young as 9 years may be vaccinated.¹

Three doses are required, with the second and third doses administered 2 and 6 months after the first. Because some providers had been administering the third dose at month 4, ACIP issued a clarification in 2008, noting that there should be a minimum of 24 weeks between the first and third dose.

MCV and MPSV. Meningococcal conjugate vaccine (MCV) is preferred over meningococcal polysaccharide vaccine (MPSV) for those 55 years of age or younger, although MPSV is an acceptable alternative. ACIP clarified recommendations for revaccination, as follows:

Individuals ages 11 to 55 years who were vaccinated with MPSV should consider revaccination with MCV after 5 years, if the risk of meningococcal meningitis persists. Children ages 2 to 10 years should be revaccinated with MCV 3 years after receiving MPSV.

Highlights of the 2008 recommendations of the CDC’s Advisory Committee on Immunization Practices (ACIP), detailed in the child and adult immunization schedules in the MMWR in January,^1,2 include:

• an expansion of the age groups for whom an annual influenza vaccine is recommended;
• expanded indications for the pneumococcal polysaccharide vaccine;
• 2 new combination vaccines for children; and
• a second rotavirus vaccine, with revised recommendations to accommodate both vaccine products.

School-age children should get flu vaccine

Children and adolescents ages 5 through 18 years are now among those who should receive an annual flu vaccine. Previously, routine vaccination was recommended only for adults and children ages 6 months through 59 months.³

Because of the timing of vaccine purchase, ACIP recognizes that routine vaccination of 5- to 18-year-olds may not be possible in some settings until next year. Family physicians who are unable to fully incorporate this new recommendation in the 2008-2009 flu season should immunize children and adolescents who are at high risk for complications of the flu. Included in that group are 5- to 18-year-olds who are on long-term aspirin therapy; have a chronic pulmonary disease, including asthma, or a cardiovascular, renal, hepatic, hematologic, or metabolic disorder; are immunosuppressed; or have a neurological or musculoskeletal disorder that alters respiratory function or the clearance of respiratory secretions. Children and adolescents who live with others at elevated risk—kids younger than 5 years, adults older than 50 years, or individuals with medical conditions that place them at high risk for severe influenza complications—should also be vaccinated.

Pneumococcal vaccine: New indications, clarifications

Two new groups have been added to the list of people for whom the 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended: asthma patients and smokers. Smoking poses as great a risk for pneumococcal pneumonia as diabetes and other chronic illnesses that had already been noted as indications for the vaccine. The number needed to vaccinate to prevent 1 case of pneumonia in smokers is 10,000 for those between the ages of 18 to 44 years, and 4000 for those ages 45 to 64 years.

A second dose. Also in 2008, ACIP clarified its dosing recommendations for PPV23: A second dose, given 5 years after the first, is recommended for those with immune suppression, sickle cell disease, or asplenia. Individuals who are 65 years of age or older should receive a second dose if they were vaccinated 5 or more years ago and were younger than 65 at the time of primary vaccination.

Not for all Native Americans. The recommendation for the use of PPV23 among the Native American population has changed, too.

Research showing high rates of invasive pneumococcal disease in Native American communities has been performed in only a few locations and cannot be generalized to all Native Americans. Therefore, ACIP has gone from recommending routine use of the vaccine among all Native Americans to a recommendation based on the same risks and age recommendations as the general population and, in communities with high rates of disease, on public health recommendations based on the incidence and epidemiology of disease.

Combination products may mean fewer injections

Two new combination vaccine products—Pentacel⁴ and Kinrix⁵—were approved last year. Both can reduce the number of injections required to complete the child immunization recommendations.

Pentacel combines 5 vaccines—diphtheria, tetanus, and pertussis (DTaP), inactivated poliovirus (IPV), and Haemophilus influenzae type b (Hib)—and is licensed for children 6 weeks through 4 years of age. Pentacel has a 4-dose schedule, with vaccine administration at 2, 4, 6, and 15 to 18 months of age. Technically, this 4-dose schedule would fulfill requirements for 4 doses of IPV. However, this could conflict with a state school immunization schedule that requires the last dose of IPV vaccine to be administered when the child is between the ages of 4 and 6 years.⁶

TABLE
Rotavirus vaccines: An administration guide

Kinrix contains DTaP and IPV. The vaccine is indicated for use as the fifth dose of DTaP and the fourth dose of IPV in children 4 through 6 years of age, following a primary series using Infanrix (DTaP) and Pediarix (DTaP, hepatitis B, and IPV).

Rotavirus vaccines: Now there are 2

There are now 2 licensed rotavirus vaccines: RotaTeq was approved in 2006,⁷ and Rotarix in 2008.⁸ ACIP does not express a preference for either product, but has revised its recommendations for rotavirus vaccination to accommodate the new release. Both RotaTeq and Rotarix are live oral vaccines, but they differ in composition and schedule of administration. Rotarix should not be given to infants who are allergic to latex, as its oral applicator contains latex rubber.

Dosing requirements. RotaTeq is administered in a 3-dose series at ages 2, 4, and 6 months; Rotarix is given in a 2-dose series at 2 and 4 months of age (TABLE). The first dose of either vaccine should be administered to children between the ages of 6 weeks and 14 weeks, 6 days. (Previously, 12 weeks was the maximum age for the first dose of rotavirus vaccine.) Neither vaccine series should be initiated in infants who are 15 weeks of age or older. The minimum interval between doses is 4 weeks, and the final dose should be administered by the age of 8 months.

It is best to complete the vaccine series with the same product. If the vaccine used initially is not available, the series can be completed with the other product, but the different number of doses required must be considered. If any dose in the series was RotaTeq or you are unable to determine which rotavirus vaccine was administered previously, a total of 3 doses should be given.

HPV and meningococcal vaccine clarification

Human papilloma virus vaccine. The HPV vaccine is recommended for all females ages 11 through 26 years, but ACIP has indicated that girls as young as 9 years may be vaccinated.¹

Three doses are required, with the second and third doses administered 2 and 6 months after the first. Because some providers had been administering the third dose at month 4, ACIP issued a clarification in 2008, noting that there should be a minimum of 24 weeks between the first and third dose.

MCV and MPSV. Meningococcal conjugate vaccine (MCV) is preferred over meningococcal polysaccharide vaccine (MPSV) for those 55 years of age or younger, although MPSV is an acceptable alternative. ACIP clarified recommendations for revaccination, as follows:

Individuals ages 11 to 55 years who were vaccinated with MPSV should consider revaccination with MCV after 5 years, if the risk of meningococcal meningitis persists. Children ages 2 to 10 years should be revaccinated with MCV 3 years after receiving MPSV.

Highlights of the 2008 recommendations of the CDC’s Advisory Committee on Immunization Practices (ACIP), detailed in the child and adult immunization schedules in the MMWR in January,^1,2 include:

• an expansion of the age groups for whom an annual influenza vaccine is recommended;
• expanded indications for the pneumococcal polysaccharide vaccine;
• 2 new combination vaccines for children; and
• a second rotavirus vaccine, with revised recommendations to accommodate both vaccine products.

School-age children should get flu vaccine

Children and adolescents ages 5 through 18 years are now among those who should receive an annual flu vaccine. Previously, routine vaccination was recommended only for adults and children ages 6 months through 59 months.³

Because of the timing of vaccine purchase, ACIP recognizes that routine vaccination of 5- to 18-year-olds may not be possible in some settings until next year. Family physicians who are unable to fully incorporate this new recommendation in the 2008-2009 flu season should immunize children and adolescents who are at high risk for complications of the flu. Included in that group are 5- to 18-year-olds who are on long-term aspirin therapy; have a chronic pulmonary disease, including asthma, or a cardiovascular, renal, hepatic, hematologic, or metabolic disorder; are immunosuppressed; or have a neurological or musculoskeletal disorder that alters respiratory function or the clearance of respiratory secretions. Children and adolescents who live with others at elevated risk—kids younger than 5 years, adults older than 50 years, or individuals with medical conditions that place them at high risk for severe influenza complications—should also be vaccinated.

Pneumococcal vaccine: New indications, clarifications

Two new groups have been added to the list of people for whom the 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended: asthma patients and smokers. Smoking poses as great a risk for pneumococcal pneumonia as diabetes and other chronic illnesses that had already been noted as indications for the vaccine. The number needed to vaccinate to prevent 1 case of pneumonia in smokers is 10,000 for those between the ages of 18 to 44 years, and 4000 for those ages 45 to 64 years.

A second dose. Also in 2008, ACIP clarified its dosing recommendations for PPV23: A second dose, given 5 years after the first, is recommended for those with immune suppression, sickle cell disease, or asplenia. Individuals who are 65 years of age or older should receive a second dose if they were vaccinated 5 or more years ago and were younger than 65 at the time of primary vaccination.

Not for all Native Americans. The recommendation for the use of PPV23 among the Native American population has changed, too.

Research showing high rates of invasive pneumococcal disease in Native American communities has been performed in only a few locations and cannot be generalized to all Native Americans. Therefore, ACIP has gone from recommending routine use of the vaccine among all Native Americans to a recommendation based on the same risks and age recommendations as the general population and, in communities with high rates of disease, on public health recommendations based on the incidence and epidemiology of disease.

Combination products may mean fewer injections

Two new combination vaccine products—Pentacel⁴ and Kinrix⁵—were approved last year. Both can reduce the number of injections required to complete the child immunization recommendations.

Pentacel combines 5 vaccines—diphtheria, tetanus, and pertussis (DTaP), inactivated poliovirus (IPV), and Haemophilus influenzae type b (Hib)—and is licensed for children 6 weeks through 4 years of age. Pentacel has a 4-dose schedule, with vaccine administration at 2, 4, 6, and 15 to 18 months of age. Technically, this 4-dose schedule would fulfill requirements for 4 doses of IPV. However, this could conflict with a state school immunization schedule that requires the last dose of IPV vaccine to be administered when the child is between the ages of 4 and 6 years.⁶

TABLE
Rotavirus vaccines: An administration guide

Kinrix contains DTaP and IPV. The vaccine is indicated for use as the fifth dose of DTaP and the fourth dose of IPV in children 4 through 6 years of age, following a primary series using Infanrix (DTaP) and Pediarix (DTaP, hepatitis B, and IPV).

Rotavirus vaccines: Now there are 2

There are now 2 licensed rotavirus vaccines: RotaTeq was approved in 2006,⁷ and Rotarix in 2008.⁸ ACIP does not express a preference for either product, but has revised its recommendations for rotavirus vaccination to accommodate the new release. Both RotaTeq and Rotarix are live oral vaccines, but they differ in composition and schedule of administration. Rotarix should not be given to infants who are allergic to latex, as its oral applicator contains latex rubber.

Dosing requirements. RotaTeq is administered in a 3-dose series at ages 2, 4, and 6 months; Rotarix is given in a 2-dose series at 2 and 4 months of age (TABLE). The first dose of either vaccine should be administered to children between the ages of 6 weeks and 14 weeks, 6 days. (Previously, 12 weeks was the maximum age for the first dose of rotavirus vaccine.) Neither vaccine series should be initiated in infants who are 15 weeks of age or older. The minimum interval between doses is 4 weeks, and the final dose should be administered by the age of 8 months.

It is best to complete the vaccine series with the same product. If the vaccine used initially is not available, the series can be completed with the other product, but the different number of doses required must be considered. If any dose in the series was RotaTeq or you are unable to determine which rotavirus vaccine was administered previously, a total of 3 doses should be given.

HPV and meningococcal vaccine clarification

Human papilloma virus vaccine. The HPV vaccine is recommended for all females ages 11 through 26 years, but ACIP has indicated that girls as young as 9 years may be vaccinated.¹

Three doses are required, with the second and third doses administered 2 and 6 months after the first. Because some providers had been administering the third dose at month 4, ACIP issued a clarification in 2008, noting that there should be a minimum of 24 weeks between the first and third dose.

MCV and MPSV. Meningococcal conjugate vaccine (MCV) is preferred over meningococcal polysaccharide vaccine (MPSV) for those 55 years of age or younger, although MPSV is an acceptable alternative. ACIP clarified recommendations for revaccination, as follows:

Individuals ages 11 to 55 years who were vaccinated with MPSV should consider revaccination with MCV after 5 years, if the risk of meningococcal meningitis persists. Children ages 2 to 10 years should be revaccinated with MCV 3 years after receiving MPSV.

When patients reached a certain age (36 for men, 46 for women), it used to mean that it was time, in the eyes of the United States Preventive Services Task Force (USPSTF), to screen for lipid disorders. But that’s changed for female patients.

The USPSTF’s latest recommendations (TABLE 1) on screening for lipid disorders in adults¹ call for screening women only when coronary heart disease (CHD) risk factors are present, regardless of their age. (See TABLE 2 for a list of CHD risk factors.) That’s a major shift from the 2001 recommendation, which stated that all women over age 45 should be screened and women ages 20 to 45 should be screened if they were at elevated risk.

The recommendations for men remain the same: All men older than 35 should be screened, as should men who are between the ages of 20 and 35 who have other CHD risks.

TABLE 1
USPSTF lipid disorder screening recommendations at a glance

TABLE 2
Risk factors for CHD

A different approach from NIH and AHA

The revised updated recommendation for women over age 45 was based on 2 systematic evidence reviews^2,3 that concluded, while treatment clearly benefits women with other risk factors, benefit has not been proven for women who are otherwise CHD risk free.

The recommendation for women conflicts with those of the National Institutes of Health and the American Heart Association; both recommend screening all adults starting at age 20—regardless of risk.

Screening those without risk isn’t ruled out

It is important to note that the task force is not recommending against screening in women (or men between the ages of 20 and 35) who do not have other CHD risks. The task force makes a C recommendation with wording that states, “The USPSTF makes no recommendation for or against routine provision of [the service]. The USPSTF found at least fair evidence that [the service] can improve health outcomes but concludes that the balance of benefits and harms is too close to justify a general recommendation” (TABLE 3).

The task force chose not to use the new wording for a C recommendation, adopted in 2007, which reads, “The USPSTF recommends against routinely providing the service. There may be considerations that support providing the service in an individual patient. There is at least moderate certainty that the net benefit is small.”

It is also important to realize that a large proportion of women have another CHD risk and will not fall into the C category recommendation.

TABLE 3
USPSTF recommendation categories

No need to look at triglycerides initially

The task force recommends screening with a fasting or nonfasting serum sample for total cholesterol and high-density lipoprotein cholesterol. The task force does not recommend including a triglyceride level because there is mixed and inclusive evidence that triglyceride levels are independently associated with CHD risk and scant evidence that treating isolated elevated triglyceride levels reduces the occurrence of CHD events. This approach also conflicts with other organizations that recommend screening with fasting lipid profiles that include a triglyceride level.

The task force states that an abnormal initial screen should be confirmed by a repeat test and, if confirmed, a fasting lipid panel should be obtained. Wide adoption of the task force recommendations would result in considerable savings in cost and patient inconvenience by avoiding complete fasting lipid panels as the initial screen.

The optimal frequency of screening is not established and the task force states that every 5 years is reasonable, although more frequent testing might be considered for those with high normal values, and less frequent intervals for those with optimal cholesterol levels and healthy lifestyles.

Treatment: Look beyond lifestyle

The screening recommendations are accompanied by a discussion of clinical considerations and a description of an approach to treatment for those with lipid disorders. The main point the task force makes is that all CHD risks should be addressed, and that lifestyle changes alone rarely reduce elevated cholesterol to an optimal level. (For more on the treatment of hyperlipidemia, see the National Heart, Lung, and Blood Institute’s Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults [Adult Treatment Panel III] at http://www.nhlbi.nih.gov/guidelines/cholesterol/index.htm.)

Time to rethink conventional opinion

The updated task force recommendations are a reminder that many widely used guidelines, including those on the prevention of CHD, are based on a lack of high-level evidence. Thus, it is not surprising that a rigorously evidence-based analysis, as preformed by the USPSTF, will frequently result in recommendations that are at variance with common practice and conventional opinion.

When patients reached a certain age (36 for men, 46 for women), it used to mean that it was time, in the eyes of the United States Preventive Services Task Force (USPSTF), to screen for lipid disorders. But that’s changed for female patients.

The USPSTF’s latest recommendations (TABLE 1) on screening for lipid disorders in adults¹ call for screening women only when coronary heart disease (CHD) risk factors are present, regardless of their age. (See TABLE 2 for a list of CHD risk factors.) That’s a major shift from the 2001 recommendation, which stated that all women over age 45 should be screened and women ages 20 to 45 should be screened if they were at elevated risk.