ID Consult

August was National Immunization Awareness Month. For most pediatricians, it is also a very busy month as patients prepare for the start of the new school year. So how are we doing?

On August 28, 2013, vaccination coverage of U.S. children aged 19-35 months was published in Morbidity and Mortality Weekly Review (2014; 63:741-8) based on results from the National Information Survey (NIS), which provides national, regional, state, and selected local area vaccination coverage estimates. NIS has monitored vaccination coverage since 1994 for all 50 states and assists in tracking the progress of achieving our national goals. It also can identify problem areas that may require special interventions. Survey data was obtained by a random telephone survey using both landline and cellular phones to households that have children born between January 2010 and May 2012. The verbal interview was followed by a survey mailed to the vaccine provider to confirm the verbal vaccine history.

Highlights

Vaccination coverage of at least 90 %, a goal of Healthy People 2020, was achieved for receipt of one or more dose of MMR (91.9%); three or more doses of hepatitis B vaccine (HepB) (90.8 %); three or more doses of poliovirus vaccine (92.7%) and one or more doses of varicella vaccine (91.2%).

Coverage for the following vaccines failed to meet this goal: four or more doses of diphtheria, tetanus, and pertussis vaccine (DTaP) (83.1%); four or more doses of pneumococcal conjugate vaccine (PCV) (82%); and a full series of Haemophilus influenzae type b (Hib) (82%). Coverage for the remaining vaccines also fell short of their respective targeted goals: two or more doses of hepatitis A vaccine (54.7%; target 85%); rotavirus (72.6%; target 80%); and hepatitis B birth dose (74.2%; target 85%).

Compared with 2012, coverage remained stable for the four vaccines that achieved at least 90% coverage. For those that did not, rotavirus was the only vaccine in 2013 that had an increase (4%) in coverage. Of note, there was an increase in the birth dose of 2.6% for Hep B.

Children living at or below the poverty level had lower vaccination coverage, compared with those living at or above this level for several vaccines, including four or more doses of DTaP; full series of Hib vaccine, four or more doses of PCV, and rotavirus vaccine. Coverage was between 8% and 12.6% points lower for these vaccines.

Measles

Let’s take a closer look at measles. Nationally, almost 92 % of children received at least one dose of MMR. However, coverage varied by state – an observation unchanged from 2012. New Hampshire had the highest coverage at 96.3% and three states had coverage of only 86% (Colorado, Ohio, and West Virginia). Overall 17 states had immunization rates less than 90%. Additionally, 1 in 12 children did not receive their first dose of MMR on time. Why the concern? In 2013, there were 187 cases of measles including 11 outbreaks. A total of 82% occurred in unvaccinated individuals, and another 9% were unaware of their immunization status.

As of Aug. 25, 2014, there were 595 cases of measles in the United States in 21 states, according to the Centers for Disease Control and Prevention’s National Center for Immunization and Respiratory Diseases. This is the highest number of cases reported since endemic measles was eliminated in 2000. There were as a result of 18 outbreaks, representing 89% of the reported cases. Cases are occurring even in states where immunization rates are reported to be at least 90% – a reminder that there can be pockets of low or nonimmunizing communities that leave its citizens vulnerable to outbreaks when a highly contagious virus is introduced.

Since endemic measles was eliminated 14 years ago in the United States, many health care providers have never seen a case of measles or may not realize the impact it once had on our public health system. Prior to the initiation of the measles vaccination program in 1963, 3-4 million cases of measles occurred annually in the United States with 400-500 deaths and 48,000 hospitalizations. Approximately another 1,000 individuals were left disabled secondary to measles encephalitis. Once the vaccine was introduced, the incidence of measles declined 98%, according to "Epidemiology and Prevention of Vaccine-Preventable Diseases," 12th ed., second printing. (Washington, D.C: Public Health Foundation, 2012). Between 1989 and 1991, there was a resurgence of measles resulting in approximately 55,000 cases, 11,000 hospitalizations, and 123 deaths. The resurgence was caused primarily by the failure to vaccinate uninsured children at the recommended 12-15 months of age. Children younger than 5 years of age accounted for 45% of all cases. The Vaccines for Children Program was created in 1993 as a direct response to the resurgence of measles. It would ensure that no child would contract a vaccine preventable disease because of inability to pay.

 

Measles remains endemic in multiple countries worldwide that are travel destinations for many Americans. In 2013, 99% of 159 U.S. cases were import related. An overwhelming majority of infections occurred in unvaccinated individuals. In 2014, this trend continues, with the majority of cases occurring in unvaccinated international travelers who return infected and spread disease to susceptible persons including children in their communities (MMWR 2014:63;496-9). Of the 288 cases reported in by May 23, 2014, 97% were associated with importations from 18 countries.

High immunization coverage must be maintained to prevent and sustain measles elimination in the United States. As a reminder, all children aged 6-11 months should receive one dose of MMR ideally 2 weeks prior to international travel. When the infant is at least 12 months of age, they should receive two additional doses of MMR or MMRV according to the routine immunization schedule. Those children older than 12 months of age should receive two doses of MMR. The second can be administered as soon as 4 weeks after the first dose. It is not uncommon for families to travel internationally and fail to mention it to you. Many have been told their child’s immunizations are up to date, not realizing that international travel may alter that definition. It behooves primary care providers to develop strategies to facilitate discussions regarding sharing international travel plans in a timely manner.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She had no relevant financial disclosures. Write to Dr. Word at [email protected].

August was National Immunization Awareness Month. For most pediatricians, it is also a very busy month as patients prepare for the start of the new school year. So how are we doing?

On August 28, 2013, vaccination coverage of U.S. children aged 19-35 months was published in Morbidity and Mortality Weekly Review (2014; 63:741-8) based on results from the National Information Survey (NIS), which provides national, regional, state, and selected local area vaccination coverage estimates. NIS has monitored vaccination coverage since 1994 for all 50 states and assists in tracking the progress of achieving our national goals. It also can identify problem areas that may require special interventions. Survey data was obtained by a random telephone survey using both landline and cellular phones to households that have children born between January 2010 and May 2012. The verbal interview was followed by a survey mailed to the vaccine provider to confirm the verbal vaccine history.

Highlights

Vaccination coverage of at least 90 %, a goal of Healthy People 2020, was achieved for receipt of one or more dose of MMR (91.9%); three or more doses of hepatitis B vaccine (HepB) (90.8 %); three or more doses of poliovirus vaccine (92.7%) and one or more doses of varicella vaccine (91.2%).

Coverage for the following vaccines failed to meet this goal: four or more doses of diphtheria, tetanus, and pertussis vaccine (DTaP) (83.1%); four or more doses of pneumococcal conjugate vaccine (PCV) (82%); and a full series of Haemophilus influenzae type b (Hib) (82%). Coverage for the remaining vaccines also fell short of their respective targeted goals: two or more doses of hepatitis A vaccine (54.7%; target 85%); rotavirus (72.6%; target 80%); and hepatitis B birth dose (74.2%; target 85%).

Compared with 2012, coverage remained stable for the four vaccines that achieved at least 90% coverage. For those that did not, rotavirus was the only vaccine in 2013 that had an increase (4%) in coverage. Of note, there was an increase in the birth dose of 2.6% for Hep B.

Children living at or below the poverty level had lower vaccination coverage, compared with those living at or above this level for several vaccines, including four or more doses of DTaP; full series of Hib vaccine, four or more doses of PCV, and rotavirus vaccine. Coverage was between 8% and 12.6% points lower for these vaccines.

Measles

Let’s take a closer look at measles. Nationally, almost 92 % of children received at least one dose of MMR. However, coverage varied by state – an observation unchanged from 2012. New Hampshire had the highest coverage at 96.3% and three states had coverage of only 86% (Colorado, Ohio, and West Virginia). Overall 17 states had immunization rates less than 90%. Additionally, 1 in 12 children did not receive their first dose of MMR on time. Why the concern? In 2013, there were 187 cases of measles including 11 outbreaks. A total of 82% occurred in unvaccinated individuals, and another 9% were unaware of their immunization status.

As of Aug. 25, 2014, there were 595 cases of measles in the United States in 21 states, according to the Centers for Disease Control and Prevention’s National Center for Immunization and Respiratory Diseases. This is the highest number of cases reported since endemic measles was eliminated in 2000. There were as a result of 18 outbreaks, representing 89% of the reported cases. Cases are occurring even in states where immunization rates are reported to be at least 90% – a reminder that there can be pockets of low or nonimmunizing communities that leave its citizens vulnerable to outbreaks when a highly contagious virus is introduced.

Since endemic measles was eliminated 14 years ago in the United States, many health care providers have never seen a case of measles or may not realize the impact it once had on our public health system. Prior to the initiation of the measles vaccination program in 1963, 3-4 million cases of measles occurred annually in the United States with 400-500 deaths and 48,000 hospitalizations. Approximately another 1,000 individuals were left disabled secondary to measles encephalitis. Once the vaccine was introduced, the incidence of measles declined 98%, according to "Epidemiology and Prevention of Vaccine-Preventable Diseases," 12th ed., second printing. (Washington, D.C: Public Health Foundation, 2012). Between 1989 and 1991, there was a resurgence of measles resulting in approximately 55,000 cases, 11,000 hospitalizations, and 123 deaths. The resurgence was caused primarily by the failure to vaccinate uninsured children at the recommended 12-15 months of age. Children younger than 5 years of age accounted for 45% of all cases. The Vaccines for Children Program was created in 1993 as a direct response to the resurgence of measles. It would ensure that no child would contract a vaccine preventable disease because of inability to pay.

 

Measles remains endemic in multiple countries worldwide that are travel destinations for many Americans. In 2013, 99% of 159 U.S. cases were import related. An overwhelming majority of infections occurred in unvaccinated individuals. In 2014, this trend continues, with the majority of cases occurring in unvaccinated international travelers who return infected and spread disease to susceptible persons including children in their communities (MMWR 2014:63;496-9). Of the 288 cases reported in by May 23, 2014, 97% were associated with importations from 18 countries.

High immunization coverage must be maintained to prevent and sustain measles elimination in the United States. As a reminder, all children aged 6-11 months should receive one dose of MMR ideally 2 weeks prior to international travel. When the infant is at least 12 months of age, they should receive two additional doses of MMR or MMRV according to the routine immunization schedule. Those children older than 12 months of age should receive two doses of MMR. The second can be administered as soon as 4 weeks after the first dose. It is not uncommon for families to travel internationally and fail to mention it to you. Many have been told their child’s immunizations are up to date, not realizing that international travel may alter that definition. It behooves primary care providers to develop strategies to facilitate discussions regarding sharing international travel plans in a timely manner.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She had no relevant financial disclosures. Write to Dr. Word at [email protected].

August was National Immunization Awareness Month. For most pediatricians, it is also a very busy month as patients prepare for the start of the new school year. So how are we doing?

On August 28, 2013, vaccination coverage of U.S. children aged 19-35 months was published in Morbidity and Mortality Weekly Review (2014; 63:741-8) based on results from the National Information Survey (NIS), which provides national, regional, state, and selected local area vaccination coverage estimates. NIS has monitored vaccination coverage since 1994 for all 50 states and assists in tracking the progress of achieving our national goals. It also can identify problem areas that may require special interventions. Survey data was obtained by a random telephone survey using both landline and cellular phones to households that have children born between January 2010 and May 2012. The verbal interview was followed by a survey mailed to the vaccine provider to confirm the verbal vaccine history.

Highlights

Vaccination coverage of at least 90 %, a goal of Healthy People 2020, was achieved for receipt of one or more dose of MMR (91.9%); three or more doses of hepatitis B vaccine (HepB) (90.8 %); three or more doses of poliovirus vaccine (92.7%) and one or more doses of varicella vaccine (91.2%).

Coverage for the following vaccines failed to meet this goal: four or more doses of diphtheria, tetanus, and pertussis vaccine (DTaP) (83.1%); four or more doses of pneumococcal conjugate vaccine (PCV) (82%); and a full series of Haemophilus influenzae type b (Hib) (82%). Coverage for the remaining vaccines also fell short of their respective targeted goals: two or more doses of hepatitis A vaccine (54.7%; target 85%); rotavirus (72.6%; target 80%); and hepatitis B birth dose (74.2%; target 85%).

Compared with 2012, coverage remained stable for the four vaccines that achieved at least 90% coverage. For those that did not, rotavirus was the only vaccine in 2013 that had an increase (4%) in coverage. Of note, there was an increase in the birth dose of 2.6% for Hep B.

Children living at or below the poverty level had lower vaccination coverage, compared with those living at or above this level for several vaccines, including four or more doses of DTaP; full series of Hib vaccine, four or more doses of PCV, and rotavirus vaccine. Coverage was between 8% and 12.6% points lower for these vaccines.

Measles

Let’s take a closer look at measles. Nationally, almost 92 % of children received at least one dose of MMR. However, coverage varied by state – an observation unchanged from 2012. New Hampshire had the highest coverage at 96.3% and three states had coverage of only 86% (Colorado, Ohio, and West Virginia). Overall 17 states had immunization rates less than 90%. Additionally, 1 in 12 children did not receive their first dose of MMR on time. Why the concern? In 2013, there were 187 cases of measles including 11 outbreaks. A total of 82% occurred in unvaccinated individuals, and another 9% were unaware of their immunization status.

As of Aug. 25, 2014, there were 595 cases of measles in the United States in 21 states, according to the Centers for Disease Control and Prevention’s National Center for Immunization and Respiratory Diseases. This is the highest number of cases reported since endemic measles was eliminated in 2000. There were as a result of 18 outbreaks, representing 89% of the reported cases. Cases are occurring even in states where immunization rates are reported to be at least 90% – a reminder that there can be pockets of low or nonimmunizing communities that leave its citizens vulnerable to outbreaks when a highly contagious virus is introduced.

Since endemic measles was eliminated 14 years ago in the United States, many health care providers have never seen a case of measles or may not realize the impact it once had on our public health system. Prior to the initiation of the measles vaccination program in 1963, 3-4 million cases of measles occurred annually in the United States with 400-500 deaths and 48,000 hospitalizations. Approximately another 1,000 individuals were left disabled secondary to measles encephalitis. Once the vaccine was introduced, the incidence of measles declined 98%, according to "Epidemiology and Prevention of Vaccine-Preventable Diseases," 12th ed., second printing. (Washington, D.C: Public Health Foundation, 2012). Between 1989 and 1991, there was a resurgence of measles resulting in approximately 55,000 cases, 11,000 hospitalizations, and 123 deaths. The resurgence was caused primarily by the failure to vaccinate uninsured children at the recommended 12-15 months of age. Children younger than 5 years of age accounted for 45% of all cases. The Vaccines for Children Program was created in 1993 as a direct response to the resurgence of measles. It would ensure that no child would contract a vaccine preventable disease because of inability to pay.

 

Measles remains endemic in multiple countries worldwide that are travel destinations for many Americans. In 2013, 99% of 159 U.S. cases were import related. An overwhelming majority of infections occurred in unvaccinated individuals. In 2014, this trend continues, with the majority of cases occurring in unvaccinated international travelers who return infected and spread disease to susceptible persons including children in their communities (MMWR 2014:63;496-9). Of the 288 cases reported in by May 23, 2014, 97% were associated with importations from 18 countries.

High immunization coverage must be maintained to prevent and sustain measles elimination in the United States. As a reminder, all children aged 6-11 months should receive one dose of MMR ideally 2 weeks prior to international travel. When the infant is at least 12 months of age, they should receive two additional doses of MMR or MMRV according to the routine immunization schedule. Those children older than 12 months of age should receive two doses of MMR. The second can be administered as soon as 4 weeks after the first dose. It is not uncommon for families to travel internationally and fail to mention it to you. Many have been told their child’s immunizations are up to date, not realizing that international travel may alter that definition. It behooves primary care providers to develop strategies to facilitate discussions regarding sharing international travel plans in a timely manner.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She had no relevant financial disclosures. Write to Dr. Word at [email protected].

The effectiveness of influenza vaccine is recognized to vary widely from season to season. At least two factors are critical for determining the likelihood that flu vaccine will be successful in preventing illness.

First, the demographics of who is being immunized (primarily age and presence of comorbidity) and second, the "match" between the circulating flu viruses and that year’s flu vaccine. When the flu vaccine is a poor match with circulating viruses, less benefit from flu vaccination will be observed; in years when the "match" between vaccine and circulating virus is good, substantial reduction in influenza respiratory illness in children and adults is observed. Recently, a second influenza B antigen has been added (creating quadrivalent vaccines) to improve the match with influenza B strains that may circulate in the community.

In February 2014, the Centers for Disease Control and Prevention reported midseason vaccine effectiveness estimates (MMWR 2014 Feb 21;63:137-42).

The major circulating virus was influenza A "2009 H1N1" virus and the "match" between vaccine strains and circulating strains was considered good. The CDC’s midseason vaccine effectiveness estimate was 61% for all age groups (95% confidence interval, 52%-68%), reinforcing the value of influenza vaccine for disease prevention in both children and adults. Flu vaccine reduced the risk of seeking medical attention for flulike illness by 60% for both children and adults.

Another factor that may determine the effectiveness of influenza vaccine in children is whether the individual receives live attenuated influenza vaccine (LAIV) or trivalent or quadrivalent inactivated influenza vaccine (IIV). The CDC has been considering the question "should LAIV be recommended preferentially over IIV in healthy children 2-8 years of age?" based on data from a limited number of studies. Canada, United Kingdom, Israel, and Germany have each expressed a preference for LAIV in their recent recommendations. The CDC working group evaluated published studies primarily restricted to those focused on healthy children, those with both LAIV and IIV cohorts, those studying the U.S. licensed and similar vaccines, and those in English. Their literature review identified five randomized trials and five additional observational studies. Lab-confirmed influenza in symptomatic children was the primary outcome; influenza related mortality and hospitalization also were considered.

The efficacy of LAIV was originally established in four randomized, placebo-controlled clinical trials. Each study was completed over two influenza seasons.

In the Belshe study (N. Engl. J. Med. 1998;338:1405-12), the efficacy compared with placebo was 93% in the first season and 100% in the second (after revaccination).

In a second study (Pediatrics 2006;118:2298-312), efficacy compared to placebo was 85% in the first season and 89% in the second (after revaccination).

Subsequently, randomized studies comparing LAIV with IIV in children younger than 8 years of age demonstrating the relative benefits of LAIV were reported (N. Engl. J. Med. 2007;356:685-96; Pediatr. Infect. Dis. J. 2006 ;25:870-9). A reduction greater than or equal to 50% in laboratory-confirmed influenza cases in the LAIV cohorts compared with the trivalent inactivated vaccine groups was observed. Greater efficacy was reported both in groups that were influenza vaccine naive as well as those with prior immunization. No reductions in hospitalization and medically-attended acute respiratory illness were reported for the LAIV cohorts; however, the quality of the data was judged to be less robust than for laboratory-confirmed disease. For children aged 9-18 years, no differences in laboratory-confirmed influenza were reported.

The mechanism for improved efficacy of LAIV in young children (2-8 years) is largely unknown. LAIV may elicit long-lasting and broader humoral and cellular responses that more closely resembles natural immunity. It also has been hypothesized that LAIV is more immunogenic than IIV as a priming vaccine, and IIV is more effective in boosting preexisting immunity. It is possible that is one explanation for why LAIV is more effective in young children, and that no differences are observed in older children and adults. It also has been suggested that LAIV may elicit an antibody that is more broadly protective against mismatched influenza strains.

In June, the Advisory Committee on Immunization Practices (ACIP) proposed new recommendations regarding the use of LAIV and IIV for young healthy children. ACIP affirmed that both LAIV and IIV are effective in prevention of influenza in children, but recommended that LAIV be used for healthy children aged 2-8 years when both vaccines are available and there are no contraindications or precautions to its use. When LAIV is not immediately available, IIV should be used. Vaccination should not be delayed to procure LAIV.

ACIP restated previous contraindications and precautions to administration of LAIV. Those with contraindications to LAIV should receive inactivated vaccine. These include:

 

• Children less than 2 years of age and adults older than 49 years of age.

• Children aged 2-17 years receiving aspirin, persons with allergic reactions to vaccine or vaccine components, pregnant women, immunosuppressed persons, and persons with egg allergy.

• Children aged 2-4 years who have had a wheezing episode noted in the medical record or whose parents report that a health care provider informed them of wheezing or asthma within the last 12 months.

• Individuals who have taken antiviral medications within the previous 48 hours.

Administration to children less than 8 years of age with chronic medical conditions (specifically those associated with increased risk of influenza complications) is considered a precaution as safety has not been established.

Immunization for all children beginning at 6 months of age is still the essential message. However, when both LAIV and IIV (trivalent [TIV] or quadrivalent inactivated influenza vaccines [QIV]) are available, the advisory committee recommended LAIV as a preference in healthy children aged 2-8 years. If only TIV or QIV is available, administration of either one is recommended as delays in receipt are of greater concern than are the differences in vaccine formulations. This recommendation, if approved by the CDC director, will not be official until it is published in the 2014-2015 influenza prevention and control recommendations in the MMWR. In anticipation of this new recommendation, the manufacturer has stated that it will be producing 18 million doses of quadrivalent LAIV for the U.S. market for the 2014-2015 season, up from the 13 million it produced last season. More information when available also will be posted on the CDC influenza website and the American Academy of Pediatrics website.

Dr. Pelton is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. He said that he had no relevant financial disclosures.

The effectiveness of influenza vaccine is recognized to vary widely from season to season. At least two factors are critical for determining the likelihood that flu vaccine will be successful in preventing illness.

First, the demographics of who is being immunized (primarily age and presence of comorbidity) and second, the "match" between the circulating flu viruses and that year’s flu vaccine. When the flu vaccine is a poor match with circulating viruses, less benefit from flu vaccination will be observed; in years when the "match" between vaccine and circulating virus is good, substantial reduction in influenza respiratory illness in children and adults is observed. Recently, a second influenza B antigen has been added (creating quadrivalent vaccines) to improve the match with influenza B strains that may circulate in the community.

In February 2014, the Centers for Disease Control and Prevention reported midseason vaccine effectiveness estimates (MMWR 2014 Feb 21;63:137-42).

The major circulating virus was influenza A "2009 H1N1" virus and the "match" between vaccine strains and circulating strains was considered good. The CDC’s midseason vaccine effectiveness estimate was 61% for all age groups (95% confidence interval, 52%-68%), reinforcing the value of influenza vaccine for disease prevention in both children and adults. Flu vaccine reduced the risk of seeking medical attention for flulike illness by 60% for both children and adults.

Another factor that may determine the effectiveness of influenza vaccine in children is whether the individual receives live attenuated influenza vaccine (LAIV) or trivalent or quadrivalent inactivated influenza vaccine (IIV). The CDC has been considering the question "should LAIV be recommended preferentially over IIV in healthy children 2-8 years of age?" based on data from a limited number of studies. Canada, United Kingdom, Israel, and Germany have each expressed a preference for LAIV in their recent recommendations. The CDC working group evaluated published studies primarily restricted to those focused on healthy children, those with both LAIV and IIV cohorts, those studying the U.S. licensed and similar vaccines, and those in English. Their literature review identified five randomized trials and five additional observational studies. Lab-confirmed influenza in symptomatic children was the primary outcome; influenza related mortality and hospitalization also were considered.

The efficacy of LAIV was originally established in four randomized, placebo-controlled clinical trials. Each study was completed over two influenza seasons.

In the Belshe study (N. Engl. J. Med. 1998;338:1405-12), the efficacy compared with placebo was 93% in the first season and 100% in the second (after revaccination).

In a second study (Pediatrics 2006;118:2298-312), efficacy compared to placebo was 85% in the first season and 89% in the second (after revaccination).

Subsequently, randomized studies comparing LAIV with IIV in children younger than 8 years of age demonstrating the relative benefits of LAIV were reported (N. Engl. J. Med. 2007;356:685-96; Pediatr. Infect. Dis. J. 2006 ;25:870-9). A reduction greater than or equal to 50% in laboratory-confirmed influenza cases in the LAIV cohorts compared with the trivalent inactivated vaccine groups was observed. Greater efficacy was reported both in groups that were influenza vaccine naive as well as those with prior immunization. No reductions in hospitalization and medically-attended acute respiratory illness were reported for the LAIV cohorts; however, the quality of the data was judged to be less robust than for laboratory-confirmed disease. For children aged 9-18 years, no differences in laboratory-confirmed influenza were reported.

The mechanism for improved efficacy of LAIV in young children (2-8 years) is largely unknown. LAIV may elicit long-lasting and broader humoral and cellular responses that more closely resembles natural immunity. It also has been hypothesized that LAIV is more immunogenic than IIV as a priming vaccine, and IIV is more effective in boosting preexisting immunity. It is possible that is one explanation for why LAIV is more effective in young children, and that no differences are observed in older children and adults. It also has been suggested that LAIV may elicit an antibody that is more broadly protective against mismatched influenza strains.

In June, the Advisory Committee on Immunization Practices (ACIP) proposed new recommendations regarding the use of LAIV and IIV for young healthy children. ACIP affirmed that both LAIV and IIV are effective in prevention of influenza in children, but recommended that LAIV be used for healthy children aged 2-8 years when both vaccines are available and there are no contraindications or precautions to its use. When LAIV is not immediately available, IIV should be used. Vaccination should not be delayed to procure LAIV.

ACIP restated previous contraindications and precautions to administration of LAIV. Those with contraindications to LAIV should receive inactivated vaccine. These include:

 

• Children less than 2 years of age and adults older than 49 years of age.

• Children aged 2-17 years receiving aspirin, persons with allergic reactions to vaccine or vaccine components, pregnant women, immunosuppressed persons, and persons with egg allergy.

• Children aged 2-4 years who have had a wheezing episode noted in the medical record or whose parents report that a health care provider informed them of wheezing or asthma within the last 12 months.

• Individuals who have taken antiviral medications within the previous 48 hours.

Administration to children less than 8 years of age with chronic medical conditions (specifically those associated with increased risk of influenza complications) is considered a precaution as safety has not been established.

Immunization for all children beginning at 6 months of age is still the essential message. However, when both LAIV and IIV (trivalent [TIV] or quadrivalent inactivated influenza vaccines [QIV]) are available, the advisory committee recommended LAIV as a preference in healthy children aged 2-8 years. If only TIV or QIV is available, administration of either one is recommended as delays in receipt are of greater concern than are the differences in vaccine formulations. This recommendation, if approved by the CDC director, will not be official until it is published in the 2014-2015 influenza prevention and control recommendations in the MMWR. In anticipation of this new recommendation, the manufacturer has stated that it will be producing 18 million doses of quadrivalent LAIV for the U.S. market for the 2014-2015 season, up from the 13 million it produced last season. More information when available also will be posted on the CDC influenza website and the American Academy of Pediatrics website.

Dr. Pelton is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. He said that he had no relevant financial disclosures.

The effectiveness of influenza vaccine is recognized to vary widely from season to season. At least two factors are critical for determining the likelihood that flu vaccine will be successful in preventing illness.

First, the demographics of who is being immunized (primarily age and presence of comorbidity) and second, the "match" between the circulating flu viruses and that year’s flu vaccine. When the flu vaccine is a poor match with circulating viruses, less benefit from flu vaccination will be observed; in years when the "match" between vaccine and circulating virus is good, substantial reduction in influenza respiratory illness in children and adults is observed. Recently, a second influenza B antigen has been added (creating quadrivalent vaccines) to improve the match with influenza B strains that may circulate in the community.

In February 2014, the Centers for Disease Control and Prevention reported midseason vaccine effectiveness estimates (MMWR 2014 Feb 21;63:137-42).

The major circulating virus was influenza A "2009 H1N1" virus and the "match" between vaccine strains and circulating strains was considered good. The CDC’s midseason vaccine effectiveness estimate was 61% for all age groups (95% confidence interval, 52%-68%), reinforcing the value of influenza vaccine for disease prevention in both children and adults. Flu vaccine reduced the risk of seeking medical attention for flulike illness by 60% for both children and adults.

Another factor that may determine the effectiveness of influenza vaccine in children is whether the individual receives live attenuated influenza vaccine (LAIV) or trivalent or quadrivalent inactivated influenza vaccine (IIV). The CDC has been considering the question "should LAIV be recommended preferentially over IIV in healthy children 2-8 years of age?" based on data from a limited number of studies. Canada, United Kingdom, Israel, and Germany have each expressed a preference for LAIV in their recent recommendations. The CDC working group evaluated published studies primarily restricted to those focused on healthy children, those with both LAIV and IIV cohorts, those studying the U.S. licensed and similar vaccines, and those in English. Their literature review identified five randomized trials and five additional observational studies. Lab-confirmed influenza in symptomatic children was the primary outcome; influenza related mortality and hospitalization also were considered.

The efficacy of LAIV was originally established in four randomized, placebo-controlled clinical trials. Each study was completed over two influenza seasons.

In the Belshe study (N. Engl. J. Med. 1998;338:1405-12), the efficacy compared with placebo was 93% in the first season and 100% in the second (after revaccination).

In a second study (Pediatrics 2006;118:2298-312), efficacy compared to placebo was 85% in the first season and 89% in the second (after revaccination).

Subsequently, randomized studies comparing LAIV with IIV in children younger than 8 years of age demonstrating the relative benefits of LAIV were reported (N. Engl. J. Med. 2007;356:685-96; Pediatr. Infect. Dis. J. 2006 ;25:870-9). A reduction greater than or equal to 50% in laboratory-confirmed influenza cases in the LAIV cohorts compared with the trivalent inactivated vaccine groups was observed. Greater efficacy was reported both in groups that were influenza vaccine naive as well as those with prior immunization. No reductions in hospitalization and medically-attended acute respiratory illness were reported for the LAIV cohorts; however, the quality of the data was judged to be less robust than for laboratory-confirmed disease. For children aged 9-18 years, no differences in laboratory-confirmed influenza were reported.

The mechanism for improved efficacy of LAIV in young children (2-8 years) is largely unknown. LAIV may elicit long-lasting and broader humoral and cellular responses that more closely resembles natural immunity. It also has been hypothesized that LAIV is more immunogenic than IIV as a priming vaccine, and IIV is more effective in boosting preexisting immunity. It is possible that is one explanation for why LAIV is more effective in young children, and that no differences are observed in older children and adults. It also has been suggested that LAIV may elicit an antibody that is more broadly protective against mismatched influenza strains.

In June, the Advisory Committee on Immunization Practices (ACIP) proposed new recommendations regarding the use of LAIV and IIV for young healthy children. ACIP affirmed that both LAIV and IIV are effective in prevention of influenza in children, but recommended that LAIV be used for healthy children aged 2-8 years when both vaccines are available and there are no contraindications or precautions to its use. When LAIV is not immediately available, IIV should be used. Vaccination should not be delayed to procure LAIV.

ACIP restated previous contraindications and precautions to administration of LAIV. Those with contraindications to LAIV should receive inactivated vaccine. These include:

 

• Children less than 2 years of age and adults older than 49 years of age.

• Children aged 2-17 years receiving aspirin, persons with allergic reactions to vaccine or vaccine components, pregnant women, immunosuppressed persons, and persons with egg allergy.

• Children aged 2-4 years who have had a wheezing episode noted in the medical record or whose parents report that a health care provider informed them of wheezing or asthma within the last 12 months.

• Individuals who have taken antiviral medications within the previous 48 hours.

Administration to children less than 8 years of age with chronic medical conditions (specifically those associated with increased risk of influenza complications) is considered a precaution as safety has not been established.

Immunization for all children beginning at 6 months of age is still the essential message. However, when both LAIV and IIV (trivalent [TIV] or quadrivalent inactivated influenza vaccines [QIV]) are available, the advisory committee recommended LAIV as a preference in healthy children aged 2-8 years. If only TIV or QIV is available, administration of either one is recommended as delays in receipt are of greater concern than are the differences in vaccine formulations. This recommendation, if approved by the CDC director, will not be official until it is published in the 2014-2015 influenza prevention and control recommendations in the MMWR. In anticipation of this new recommendation, the manufacturer has stated that it will be producing 18 million doses of quadrivalent LAIV for the U.S. market for the 2014-2015 season, up from the 13 million it produced last season. More information when available also will be posted on the CDC influenza website and the American Academy of Pediatrics website.

Dr. Pelton is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. He said that he had no relevant financial disclosures.

The RIVUR [Randomized Intervention for Children With Vesicoureteral Reflux] trial investigators set out to reevaluate the role of antimicrobial prophylaxis for the prevention of recurrences in children with vesicoureteral reflux. As recent randomized trials have produced conflicting results, the goal of the RIVUR investigators was to determine whether antimicrobial prophylaxis could prevent febrile or symptomatic urinary tract infection and whether prevention would reduce the likelihood of subsequent renal scarring. The results, recently published in the New England Journal of Medicine (2014;370:2367-76), demonstrated that nearly 18% of children, 2 months to 6 years of age, have a febrile or symptomatic recurrence within the first year after the initial or presenting episode. The recurrence rate for febrile or symptomatic episodes was reduced by approximately 50% in the treatment group (trimethoprim-sulfamethoxazole) to nearly 8%.

In addition, the proportion of children considered treatment failures (defined as a combination of febrile or symptomatic UTIs or development of new renal scarring) occurred twice as often in the placebo group as in the treatment group. However, despite the reduction in febrile or symptomatic episodes in the treatment group, approximately 8% of children in both treatment and placebo groups developed new renal scarring, as defined by a decreased uptake of tracer or cortical thinning.

The study confirmed that children with higher grades of reflux (III or IV at baseline) were more likely to have febrile or symptomatic recurrences, that children with bladder and bowel dysfunction (based on a modified Dysfunctional Voiding Symptom Score) also were more likely to have febrile or symptomatic recurrences, and that recurrences in children on prophylaxis were more likely to be resistant to trimethoprim-sulfamethoxazole than were those in children on placebo.

Implications for prevention of UTI

The American Academy of Pediatrics guidelines for the management of UTI in children were updated in 2011 (Pediatrics 2011;128:595-610). The authors contacted the six researchers who had conducted the most recent randomized controlled trials and completed a formal meta-analysis that did not detect a statistically significant benefit of prophylaxis for stopping the recurrence of febrile UTI/pyelonephritis in infants without reflux or those with grades I, II, III, or IV. The 2011 recommendations reflected the findings of an AAP subcommittee that antimicrobial prophylaxis was not effective, as had been presumed in a 1999 report (Pediatrics 1999;103:843-52).

The AAP subcommittee on urinary tract infection of the Steering Committee on Quality Improvement and Management – authors of the 2011 revised guidelines – have recently reviewed the RIVUR study data (AAP News, July 1 2014) and concluded that antimicrobial prophylaxis did not alter the development of new renal scarring/damage, that the benefits of daily antimicrobial prophylaxis were modest, and that the increased likelihood of resistance to trimethoprim-sulfamethoxazole at recurrences was significant. The subcommittee reaffirmed the 2011 guidance concerning a "less aggressive" approach: Renal and bladder ultrasound are adequate for assessment of risk for renal scarring at first episodes, and watchful waiting without performing voiding cystourethrography (VCUG) or initiating prophylaxis is appropriate. VCUG is indicated after a first episode if renal and bladder ultrasonography reveals hydronephrosis, scarring, or other findings that would suggest either high-grade vesicoureteral reflux (VUR) or obstructive uropathy and in other atypical or complex clinical circumstances. As well, VCUG also should be performed if there is a recurrence of a febrile UTI (Pediatrics 2011;128:595-610).

The current subcommittee opined that prompt diagnosis and effective treatment of a febrile UTI recurrence may be of greater importance, regardless of whether VUR is present or the child is receiving antimicrobial prophylaxis.

My take

For me, the RIVUR data provide further insights into both the risk of any recurrence (approximately 18% by 12 months, approximately 25% by 24 months) and the risk for multiple recurrences (approximately 10%). The data identify those at highest risk for recurrences (patients with bladder and bowel dysfunction or higher grades of reflux) and provide evidence that trimethoprim-sulfamethoxazole prophylaxis is highly effective in such groups. No serious side effects were observed during the RIVUR trial; however, Stevens-Johnson syndrome is documented to occur rarely after administration of trimethoprim-sulfamethoxazole, and the potential for this life-threatening event should be part of the decision process. I believe the value of the new data is that they provide confidence that antimicrobial prophylaxis can be effective for the prevention of febrile/symptomatic UTI, and that in select children at great risk for recurrences and subsequent renal damage, antimicrobial prophylaxis can be part of our toolbox.

Dr. Pelton is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. He said that he had no relevant financial disclosures.

The RIVUR [Randomized Intervention for Children With Vesicoureteral Reflux] trial investigators set out to reevaluate the role of antimicrobial prophylaxis for the prevention of recurrences in children with vesicoureteral reflux. As recent randomized trials have produced conflicting results, the goal of the RIVUR investigators was to determine whether antimicrobial prophylaxis could prevent febrile or symptomatic urinary tract infection and whether prevention would reduce the likelihood of subsequent renal scarring. The results, recently published in the New England Journal of Medicine (2014;370:2367-76), demonstrated that nearly 18% of children, 2 months to 6 years of age, have a febrile or symptomatic recurrence within the first year after the initial or presenting episode. The recurrence rate for febrile or symptomatic episodes was reduced by approximately 50% in the treatment group (trimethoprim-sulfamethoxazole) to nearly 8%.

In addition, the proportion of children considered treatment failures (defined as a combination of febrile or symptomatic UTIs or development of new renal scarring) occurred twice as often in the placebo group as in the treatment group. However, despite the reduction in febrile or symptomatic episodes in the treatment group, approximately 8% of children in both treatment and placebo groups developed new renal scarring, as defined by a decreased uptake of tracer or cortical thinning.

The study confirmed that children with higher grades of reflux (III or IV at baseline) were more likely to have febrile or symptomatic recurrences, that children with bladder and bowel dysfunction (based on a modified Dysfunctional Voiding Symptom Score) also were more likely to have febrile or symptomatic recurrences, and that recurrences in children on prophylaxis were more likely to be resistant to trimethoprim-sulfamethoxazole than were those in children on placebo.

Implications for prevention of UTI

The American Academy of Pediatrics guidelines for the management of UTI in children were updated in 2011 (Pediatrics 2011;128:595-610). The authors contacted the six researchers who had conducted the most recent randomized controlled trials and completed a formal meta-analysis that did not detect a statistically significant benefit of prophylaxis for stopping the recurrence of febrile UTI/pyelonephritis in infants without reflux or those with grades I, II, III, or IV. The 2011 recommendations reflected the findings of an AAP subcommittee that antimicrobial prophylaxis was not effective, as had been presumed in a 1999 report (Pediatrics 1999;103:843-52).

The AAP subcommittee on urinary tract infection of the Steering Committee on Quality Improvement and Management – authors of the 2011 revised guidelines – have recently reviewed the RIVUR study data (AAP News, July 1 2014) and concluded that antimicrobial prophylaxis did not alter the development of new renal scarring/damage, that the benefits of daily antimicrobial prophylaxis were modest, and that the increased likelihood of resistance to trimethoprim-sulfamethoxazole at recurrences was significant. The subcommittee reaffirmed the 2011 guidance concerning a "less aggressive" approach: Renal and bladder ultrasound are adequate for assessment of risk for renal scarring at first episodes, and watchful waiting without performing voiding cystourethrography (VCUG) or initiating prophylaxis is appropriate. VCUG is indicated after a first episode if renal and bladder ultrasonography reveals hydronephrosis, scarring, or other findings that would suggest either high-grade vesicoureteral reflux (VUR) or obstructive uropathy and in other atypical or complex clinical circumstances. As well, VCUG also should be performed if there is a recurrence of a febrile UTI (Pediatrics 2011;128:595-610).

The current subcommittee opined that prompt diagnosis and effective treatment of a febrile UTI recurrence may be of greater importance, regardless of whether VUR is present or the child is receiving antimicrobial prophylaxis.

My take

For me, the RIVUR data provide further insights into both the risk of any recurrence (approximately 18% by 12 months, approximately 25% by 24 months) and the risk for multiple recurrences (approximately 10%). The data identify those at highest risk for recurrences (patients with bladder and bowel dysfunction or higher grades of reflux) and provide evidence that trimethoprim-sulfamethoxazole prophylaxis is highly effective in such groups. No serious side effects were observed during the RIVUR trial; however, Stevens-Johnson syndrome is documented to occur rarely after administration of trimethoprim-sulfamethoxazole, and the potential for this life-threatening event should be part of the decision process. I believe the value of the new data is that they provide confidence that antimicrobial prophylaxis can be effective for the prevention of febrile/symptomatic UTI, and that in select children at great risk for recurrences and subsequent renal damage, antimicrobial prophylaxis can be part of our toolbox.

Dr. Pelton is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. He said that he had no relevant financial disclosures.

The RIVUR [Randomized Intervention for Children With Vesicoureteral Reflux] trial investigators set out to reevaluate the role of antimicrobial prophylaxis for the prevention of recurrences in children with vesicoureteral reflux. As recent randomized trials have produced conflicting results, the goal of the RIVUR investigators was to determine whether antimicrobial prophylaxis could prevent febrile or symptomatic urinary tract infection and whether prevention would reduce the likelihood of subsequent renal scarring. The results, recently published in the New England Journal of Medicine (2014;370:2367-76), demonstrated that nearly 18% of children, 2 months to 6 years of age, have a febrile or symptomatic recurrence within the first year after the initial or presenting episode. The recurrence rate for febrile or symptomatic episodes was reduced by approximately 50% in the treatment group (trimethoprim-sulfamethoxazole) to nearly 8%.

In addition, the proportion of children considered treatment failures (defined as a combination of febrile or symptomatic UTIs or development of new renal scarring) occurred twice as often in the placebo group as in the treatment group. However, despite the reduction in febrile or symptomatic episodes in the treatment group, approximately 8% of children in both treatment and placebo groups developed new renal scarring, as defined by a decreased uptake of tracer or cortical thinning.

The study confirmed that children with higher grades of reflux (III or IV at baseline) were more likely to have febrile or symptomatic recurrences, that children with bladder and bowel dysfunction (based on a modified Dysfunctional Voiding Symptom Score) also were more likely to have febrile or symptomatic recurrences, and that recurrences in children on prophylaxis were more likely to be resistant to trimethoprim-sulfamethoxazole than were those in children on placebo.

Implications for prevention of UTI

The American Academy of Pediatrics guidelines for the management of UTI in children were updated in 2011 (Pediatrics 2011;128:595-610). The authors contacted the six researchers who had conducted the most recent randomized controlled trials and completed a formal meta-analysis that did not detect a statistically significant benefit of prophylaxis for stopping the recurrence of febrile UTI/pyelonephritis in infants without reflux or those with grades I, II, III, or IV. The 2011 recommendations reflected the findings of an AAP subcommittee that antimicrobial prophylaxis was not effective, as had been presumed in a 1999 report (Pediatrics 1999;103:843-52).

The AAP subcommittee on urinary tract infection of the Steering Committee on Quality Improvement and Management – authors of the 2011 revised guidelines – have recently reviewed the RIVUR study data (AAP News, July 1 2014) and concluded that antimicrobial prophylaxis did not alter the development of new renal scarring/damage, that the benefits of daily antimicrobial prophylaxis were modest, and that the increased likelihood of resistance to trimethoprim-sulfamethoxazole at recurrences was significant. The subcommittee reaffirmed the 2011 guidance concerning a "less aggressive" approach: Renal and bladder ultrasound are adequate for assessment of risk for renal scarring at first episodes, and watchful waiting without performing voiding cystourethrography (VCUG) or initiating prophylaxis is appropriate. VCUG is indicated after a first episode if renal and bladder ultrasonography reveals hydronephrosis, scarring, or other findings that would suggest either high-grade vesicoureteral reflux (VUR) or obstructive uropathy and in other atypical or complex clinical circumstances. As well, VCUG also should be performed if there is a recurrence of a febrile UTI (Pediatrics 2011;128:595-610).

The current subcommittee opined that prompt diagnosis and effective treatment of a febrile UTI recurrence may be of greater importance, regardless of whether VUR is present or the child is receiving antimicrobial prophylaxis.

My take

For me, the RIVUR data provide further insights into both the risk of any recurrence (approximately 18% by 12 months, approximately 25% by 24 months) and the risk for multiple recurrences (approximately 10%). The data identify those at highest risk for recurrences (patients with bladder and bowel dysfunction or higher grades of reflux) and provide evidence that trimethoprim-sulfamethoxazole prophylaxis is highly effective in such groups. No serious side effects were observed during the RIVUR trial; however, Stevens-Johnson syndrome is documented to occur rarely after administration of trimethoprim-sulfamethoxazole, and the potential for this life-threatening event should be part of the decision process. I believe the value of the new data is that they provide confidence that antimicrobial prophylaxis can be effective for the prevention of febrile/symptomatic UTI, and that in select children at great risk for recurrences and subsequent renal damage, antimicrobial prophylaxis can be part of our toolbox.

Dr. Pelton is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. He said that he had no relevant financial disclosures.

Recently the American Academy of Pediatrics issued recommendations that address management of asymptomatic newborns whose mothers have active herpes simplex virus (HSV) lesions noted at the time of delivery. Implementing these recommendations requires proactive coordination between the director of the laboratory and the obstetrical and pediatric providers to ensure success (Pediatrics 2013;131:e635-46).

Approximately 1,500 infants are diagnosed and treated for neonatal HSV infection each year in the United States. Most pediatricians are knowledgeable about the three forms of neonatal HSV infection and the role of prompt diagnosis and utilization of acyclovir. Even so, the outcomes of this disease may be devastating. Skin–eye–mucous membrane disease has the best prognosis (98% neurologically normal), as finding the culprit lesion generally ensures timely diagnosis and treatment. With central nervous system infection or disseminated disease, a skin lesion is not noted in 25%-40% of cases. So the diagnosis is sometimes delayed or missed initially because the initial presentations (seizures in CNS infection; sepsis picture or liver failure in disseminated disease) may sidetrack the provider into considering other working diagnoses, such as bacterial sepsis or metabolic disease. Neurologic sequelae occur in 25% of those with disseminated infection, but in upward of 70% in those with CNS disease.

Ideally, both the obstetrician and the pediatric provider play a role in ensuring appropriate care for the baby whose mother has active HSV lesions at time of delivery. Appropriate care includes preemptive treatment for neonatal HSV infection, which has the potential to improve outcomes and so should be a high priority for all providers.

The new guidance is evidence based and predicated on the availability of HSV typing of the HSV from the maternal lesion and type-specific serology. It allows the provider to define the newborn risk of acquiring HSV infection more explicitly and utilize preemptive evaluation/therapy. Providers should ensure that their hospital laboratory can perform such testing with reasonable turnaround time for results.

Obstetrical role and implications of testing

The obstetric provider should swab the maternal lesion for HSV polymerase chain reaction (PCR) assay/culture and typing (HSV-1 or HSV-2). These data can be utilized with maternal history and serologic results to calculate the neonatal risk for infection.

Calculation of relative neonatal risk

• First episode, primary infection. Defined as the first maternal HSV episode with type-specific serology being negative, this makes the risk of neonatal infection approximately 50%. If maternal history of prior disease is negative AND either the maternal lesion test results or serology results are unavailable, follow the plan of care for first episode primary infection.

• First episode, nonprimary infection. Defined as the first maternal episode but antibody to detected HSV type is not present (e.g., HSV-2 confirmed from lesion, with type 1 but NOT type 2 maternal antibody present; OR HSV-1 confirmed, with type 2 but NOT type 1 maternal antibody present), the risk of neonatal infection is approximately 25%.

• Recurrent. If the mother has a history of genital herpes and the mother’s type-specific antibody is the same as the type detected in the lesions, the risk for neonatal infection is lower and approximately 2%.

Pediatrician’s role and plan of care

The first order of business is to identify neonates who demonstrate signs or symptoms suggestive of HSV infection at birth or in the perinatal period (whether or not any lesions were noted at time of delivery). In this case, all infants should undergo full evaluation for both viral and bacterial causes and should have prompt initiation of preemptive antiviral and antibacterial therapy. The evaluation of an ill-appearing infant at birth should include CBC; liver function studies; blood, urine, and cerebrospinal fluid examination with bacterial cultures of blood, urine, and cerebrospinal fluid, plus blood and cerebrospinal fluid HSV PCR. Also, HSV surface (conjunctivae, nasopharynx, and rectum) and lesion cultures are needed. Infectious disease consultation is recommended if HSV infection is confirmed. Acyclovir should continue for 14 days for skin–eye–mucous membrane disease or 21 days for CNS or disseminated infection. Further evaluation toward the end of therapy can determine if a longer course of therapy should be considered.

The recent guideline addresses care for those infants who are born to mothers with active HSV lesions noted at time of delivery, and should be initiated only if the infant is asymptomatic at birth.

In this situation, for babies whose mothers have primary infection (risk 50% for neonatal infection) or first episode, nonprimary infection (risk 25% for neonatal infection):

• Approximately 24 hours after the infant’s birth, obtain blood HSV DNA PCR and HSV surface cultures of conjunctivae, nasopharynx, and rectum as well as from the scalp electrode site if there was one.

 

• Cerebrospinal fluid examination with HSV DNA PCR testing should be obtained.

• Acyclovir (20 mg/kg per dose every 8 hours IV) should be initiated. Preemptive therapy (acyclovir 20 mg/kg per dose every 8 hours IV) should be continued for 10 days and until all studies are negative.

For babies whose mothers have recurrent infection:

• Cerebrospinal fluid examination may be deferred.

• But the rest of the workup should be completed and IV acyclovir initiated.

• IV acyclovir can be stopped at the time that studies are negative (usually at 48 hours, assuming negative results of blood PCR and preliminary negative surface cultures), with close follow-up of the infant.

Use of this guideline can improve care of infants only when the laboratory and the obstetrical and pediatric providers have established a good working relationship. This ensures the availability of necessary HSV studies, complete implementation, and proper interpretation of testing to guide the newborn’s care.

Dr. Jackson is chief of pediatric infectious diseases at Children’s Mercy Hospital, Kansas City, Mo., and professor of pediatrics at the University of Missouri–Kansas City. Dr. Jackson was a member of the AAP Committee on Infectious Diseases who wrote the AAP clinical report entitled "Guidance on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions," but said she had no other conflicts of interest to disclose. E-mail her at [email protected].

Recently the American Academy of Pediatrics issued recommendations that address management of asymptomatic newborns whose mothers have active herpes simplex virus (HSV) lesions noted at the time of delivery. Implementing these recommendations requires proactive coordination between the director of the laboratory and the obstetrical and pediatric providers to ensure success (Pediatrics 2013;131:e635-46).

Approximately 1,500 infants are diagnosed and treated for neonatal HSV infection each year in the United States. Most pediatricians are knowledgeable about the three forms of neonatal HSV infection and the role of prompt diagnosis and utilization of acyclovir. Even so, the outcomes of this disease may be devastating. Skin–eye–mucous membrane disease has the best prognosis (98% neurologically normal), as finding the culprit lesion generally ensures timely diagnosis and treatment. With central nervous system infection or disseminated disease, a skin lesion is not noted in 25%-40% of cases. So the diagnosis is sometimes delayed or missed initially because the initial presentations (seizures in CNS infection; sepsis picture or liver failure in disseminated disease) may sidetrack the provider into considering other working diagnoses, such as bacterial sepsis or metabolic disease. Neurologic sequelae occur in 25% of those with disseminated infection, but in upward of 70% in those with CNS disease.

Ideally, both the obstetrician and the pediatric provider play a role in ensuring appropriate care for the baby whose mother has active HSV lesions at time of delivery. Appropriate care includes preemptive treatment for neonatal HSV infection, which has the potential to improve outcomes and so should be a high priority for all providers.

The new guidance is evidence based and predicated on the availability of HSV typing of the HSV from the maternal lesion and type-specific serology. It allows the provider to define the newborn risk of acquiring HSV infection more explicitly and utilize preemptive evaluation/therapy. Providers should ensure that their hospital laboratory can perform such testing with reasonable turnaround time for results.

Obstetrical role and implications of testing

The obstetric provider should swab the maternal lesion for HSV polymerase chain reaction (PCR) assay/culture and typing (HSV-1 or HSV-2). These data can be utilized with maternal history and serologic results to calculate the neonatal risk for infection.

Calculation of relative neonatal risk

• First episode, primary infection. Defined as the first maternal HSV episode with type-specific serology being negative, this makes the risk of neonatal infection approximately 50%. If maternal history of prior disease is negative AND either the maternal lesion test results or serology results are unavailable, follow the plan of care for first episode primary infection.

• First episode, nonprimary infection. Defined as the first maternal episode but antibody to detected HSV type is not present (e.g., HSV-2 confirmed from lesion, with type 1 but NOT type 2 maternal antibody present; OR HSV-1 confirmed, with type 2 but NOT type 1 maternal antibody present), the risk of neonatal infection is approximately 25%.

• Recurrent. If the mother has a history of genital herpes and the mother’s type-specific antibody is the same as the type detected in the lesions, the risk for neonatal infection is lower and approximately 2%.

Pediatrician’s role and plan of care

The first order of business is to identify neonates who demonstrate signs or symptoms suggestive of HSV infection at birth or in the perinatal period (whether or not any lesions were noted at time of delivery). In this case, all infants should undergo full evaluation for both viral and bacterial causes and should have prompt initiation of preemptive antiviral and antibacterial therapy. The evaluation of an ill-appearing infant at birth should include CBC; liver function studies; blood, urine, and cerebrospinal fluid examination with bacterial cultures of blood, urine, and cerebrospinal fluid, plus blood and cerebrospinal fluid HSV PCR. Also, HSV surface (conjunctivae, nasopharynx, and rectum) and lesion cultures are needed. Infectious disease consultation is recommended if HSV infection is confirmed. Acyclovir should continue for 14 days for skin–eye–mucous membrane disease or 21 days for CNS or disseminated infection. Further evaluation toward the end of therapy can determine if a longer course of therapy should be considered.

The recent guideline addresses care for those infants who are born to mothers with active HSV lesions noted at time of delivery, and should be initiated only if the infant is asymptomatic at birth.

In this situation, for babies whose mothers have primary infection (risk 50% for neonatal infection) or first episode, nonprimary infection (risk 25% for neonatal infection):

• Approximately 24 hours after the infant’s birth, obtain blood HSV DNA PCR and HSV surface cultures of conjunctivae, nasopharynx, and rectum as well as from the scalp electrode site if there was one.

 

• Cerebrospinal fluid examination with HSV DNA PCR testing should be obtained.

• Acyclovir (20 mg/kg per dose every 8 hours IV) should be initiated. Preemptive therapy (acyclovir 20 mg/kg per dose every 8 hours IV) should be continued for 10 days and until all studies are negative.

For babies whose mothers have recurrent infection:

• Cerebrospinal fluid examination may be deferred.

• But the rest of the workup should be completed and IV acyclovir initiated.

• IV acyclovir can be stopped at the time that studies are negative (usually at 48 hours, assuming negative results of blood PCR and preliminary negative surface cultures), with close follow-up of the infant.

Use of this guideline can improve care of infants only when the laboratory and the obstetrical and pediatric providers have established a good working relationship. This ensures the availability of necessary HSV studies, complete implementation, and proper interpretation of testing to guide the newborn’s care.

Dr. Jackson is chief of pediatric infectious diseases at Children’s Mercy Hospital, Kansas City, Mo., and professor of pediatrics at the University of Missouri–Kansas City. Dr. Jackson was a member of the AAP Committee on Infectious Diseases who wrote the AAP clinical report entitled "Guidance on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions," but said she had no other conflicts of interest to disclose. E-mail her at [email protected].

Recently the American Academy of Pediatrics issued recommendations that address management of asymptomatic newborns whose mothers have active herpes simplex virus (HSV) lesions noted at the time of delivery. Implementing these recommendations requires proactive coordination between the director of the laboratory and the obstetrical and pediatric providers to ensure success (Pediatrics 2013;131:e635-46).

Approximately 1,500 infants are diagnosed and treated for neonatal HSV infection each year in the United States. Most pediatricians are knowledgeable about the three forms of neonatal HSV infection and the role of prompt diagnosis and utilization of acyclovir. Even so, the outcomes of this disease may be devastating. Skin–eye–mucous membrane disease has the best prognosis (98% neurologically normal), as finding the culprit lesion generally ensures timely diagnosis and treatment. With central nervous system infection or disseminated disease, a skin lesion is not noted in 25%-40% of cases. So the diagnosis is sometimes delayed or missed initially because the initial presentations (seizures in CNS infection; sepsis picture or liver failure in disseminated disease) may sidetrack the provider into considering other working diagnoses, such as bacterial sepsis or metabolic disease. Neurologic sequelae occur in 25% of those with disseminated infection, but in upward of 70% in those with CNS disease.

Ideally, both the obstetrician and the pediatric provider play a role in ensuring appropriate care for the baby whose mother has active HSV lesions at time of delivery. Appropriate care includes preemptive treatment for neonatal HSV infection, which has the potential to improve outcomes and so should be a high priority for all providers.

The new guidance is evidence based and predicated on the availability of HSV typing of the HSV from the maternal lesion and type-specific serology. It allows the provider to define the newborn risk of acquiring HSV infection more explicitly and utilize preemptive evaluation/therapy. Providers should ensure that their hospital laboratory can perform such testing with reasonable turnaround time for results.

Obstetrical role and implications of testing

The obstetric provider should swab the maternal lesion for HSV polymerase chain reaction (PCR) assay/culture and typing (HSV-1 or HSV-2). These data can be utilized with maternal history and serologic results to calculate the neonatal risk for infection.

Calculation of relative neonatal risk

• First episode, primary infection. Defined as the first maternal HSV episode with type-specific serology being negative, this makes the risk of neonatal infection approximately 50%. If maternal history of prior disease is negative AND either the maternal lesion test results or serology results are unavailable, follow the plan of care for first episode primary infection.

• First episode, nonprimary infection. Defined as the first maternal episode but antibody to detected HSV type is not present (e.g., HSV-2 confirmed from lesion, with type 1 but NOT type 2 maternal antibody present; OR HSV-1 confirmed, with type 2 but NOT type 1 maternal antibody present), the risk of neonatal infection is approximately 25%.

• Recurrent. If the mother has a history of genital herpes and the mother’s type-specific antibody is the same as the type detected in the lesions, the risk for neonatal infection is lower and approximately 2%.

Pediatrician’s role and plan of care

The first order of business is to identify neonates who demonstrate signs or symptoms suggestive of HSV infection at birth or in the perinatal period (whether or not any lesions were noted at time of delivery). In this case, all infants should undergo full evaluation for both viral and bacterial causes and should have prompt initiation of preemptive antiviral and antibacterial therapy. The evaluation of an ill-appearing infant at birth should include CBC; liver function studies; blood, urine, and cerebrospinal fluid examination with bacterial cultures of blood, urine, and cerebrospinal fluid, plus blood and cerebrospinal fluid HSV PCR. Also, HSV surface (conjunctivae, nasopharynx, and rectum) and lesion cultures are needed. Infectious disease consultation is recommended if HSV infection is confirmed. Acyclovir should continue for 14 days for skin–eye–mucous membrane disease or 21 days for CNS or disseminated infection. Further evaluation toward the end of therapy can determine if a longer course of therapy should be considered.

The recent guideline addresses care for those infants who are born to mothers with active HSV lesions noted at time of delivery, and should be initiated only if the infant is asymptomatic at birth.

In this situation, for babies whose mothers have primary infection (risk 50% for neonatal infection) or first episode, nonprimary infection (risk 25% for neonatal infection):

• Approximately 24 hours after the infant’s birth, obtain blood HSV DNA PCR and HSV surface cultures of conjunctivae, nasopharynx, and rectum as well as from the scalp electrode site if there was one.

 

• Cerebrospinal fluid examination with HSV DNA PCR testing should be obtained.

• Acyclovir (20 mg/kg per dose every 8 hours IV) should be initiated. Preemptive therapy (acyclovir 20 mg/kg per dose every 8 hours IV) should be continued for 10 days and until all studies are negative.

For babies whose mothers have recurrent infection:

• Cerebrospinal fluid examination may be deferred.

• But the rest of the workup should be completed and IV acyclovir initiated.

• IV acyclovir can be stopped at the time that studies are negative (usually at 48 hours, assuming negative results of blood PCR and preliminary negative surface cultures), with close follow-up of the infant.

Use of this guideline can improve care of infants only when the laboratory and the obstetrical and pediatric providers have established a good working relationship. This ensures the availability of necessary HSV studies, complete implementation, and proper interpretation of testing to guide the newborn’s care.

Dr. Jackson is chief of pediatric infectious diseases at Children’s Mercy Hospital, Kansas City, Mo., and professor of pediatrics at the University of Missouri–Kansas City. Dr. Jackson was a member of the AAP Committee on Infectious Diseases who wrote the AAP clinical report entitled "Guidance on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions," but said she had no other conflicts of interest to disclose. E-mail her at [email protected].

School’s out for the summer soon! Many of your patients may have plans to travel to areas where they may be exposed to infectious diseases and other health risks not routinely encountered in the United States. They will join the 29 million Americans, including almost 3 million children, who traveled to overseas destinations in 2013. The potential for exposures to these risks is dependent on several factors, including the traveler’s age, health and immunization status, destination, accommodations, and duration of travel. Leisure travel, including visiting friends and relatives, accounts for approximately 90% of overseas travel. Some adolescents are traveling to resource-limited areas for adventure travel, educational experiences, and volunteerism. Many times they will reside with host families as part of this experience. There are also children who will have prolonged stays as a result of parental job relocation.

Unfortunately, health precautions often are not considered as many make their travel arrangements. International trips on average are planned at least 105 days in advance; however, many patients wait until the last minute to seek medical advice, if at all. Of 10,032 ill persons who sought post-travel evaluations at participating surveillance facilities (U.S. GeoSentinel sites) between 1997 and 2011, less than half (44%) reported seeking pretravel advice (MMWR 2013;62(SS03):1-15).

Here are some tips that should be useful and easy to implement in your practice for your internationally traveling patients.

• Make sure routine immunizations are up-to-date for age. The exception to this rule is for measles. All children at least 12 months age should receive two doses of MMR prior to departure regardless of their international destination. The second dose of MMR can be administered as early as 4 weeks after the first. Children between 6 and 11 months of age should receive a single dose of MMR prior to departure. If the initial dose is administered at less than 12 months of age, two additional doses will need to be administered to complete the series beginning at 12 months of age.

While measles is no longer endemic in the United States, as of April 25, 2014, there have been 154 cases reported from 14 states. (See measles graphic.) The majority of cases were imported by unvaccinated travelers who became ill after returning home and exposed susceptible individuals. In the last few years, most of the U.S. cases were imported from Western Europe. Currently, there are several countries experiencing record numbers of cases, including Vietnam (3,700) and the Philippines (26,000). This is not to imply that ongoing international outbreaks are limited to these two countries. For additional information, go to cdc.gov/measles.

• Identify someone in your area as a local resource for travel-related information and referrals. Make sure they are willing to see children. Develop a system to send out reminders to families to seek pretravel advice, ideally at least 1 month prior to departure. For children with chronic diseases or compromised immune systems, destination selection may need to be adjusted depending on their medical needs, availability of comparable health care at the overseas destination, and ability to receive pretravel vaccine interventions. Involvement prior to booking the trip would be advisable. Many offices successfully send out reminders for well visits and influenza vaccine. Consider incorporating one for overseas travel.

• The timing of initiation of antimalarial prophylaxis is dependent on the medication. Weekly medications such as chloroquine and mefloquine should begin at least 2 weeks prior to exposure. Atovaquone/proguanil and doxycycline are two drugs that are administered daily, and travelers can begin as late as 2 days prior to entry into a malaria-endemic area. This is a great option for the last-minute traveler.

However, there are contraindications for the use of each drug. Some are age dependent, while others are directly related to the presence of a specific medical condition. Areas where chloroquine-sensitive malaria is present are limited. It is always important to prescribe a prophylactic antimalarial agent, but even more prudent to prescribe the appropriate drug and dosage.

Not sure which drug is most appropriate for your patient? Refer to your local travel medicine expert, or visit cdc.gov/malaria.

• The accompanying table lists vaccines that are traditionally considered to be travel vaccines, but pediatricians and family physicians might not consider all to belong in that group. Most are not required for entry into a specific country, but are recommended based on the risk for potential exposure and disease acquisition. In contrast, yellow fever and meningococcal vaccines are required for entry into certain countries. Yellow fever vaccine can be administered only at authorized sites and should be received at least 10 days prior to arrival at the destination. As with routinely administered vaccines, occasionally there are shortages of travel-related vaccines. Most recently, a shortage of yellow fever vaccine has been resolved.

 

The majority of vaccines should be administered at least 2 weeks prior to departure, while others, such as rabies and Japanese encephalitis, take at least 28 days to complete the series. These are a few additional reasons it behooves your patients to seek advice early.

Travel updates

Chikungunya virus (CHIK V). Local transmission in the Americas was first reported from St. Martin in December 2013. As of May 5, 2014, a total of 12 Caribbean countries have reported locally acquired cases. The disease is transmitted by Aedes species, which are the same species that transmit dengue fever. Disease is characterized by sudden onset of high fever with severe polyarthralgia. Additional symptoms can include headache, myalgias, rash, nausea, and vomiting. Epidemics have historically occurred in Africa, Asia, and islands in the Indian Ocean. Outbreaks also have occurred in Italy and France.

There is no preventive vaccine or drug available. Treatment is symptomatic care. The disease is best prevented by taking adequate mosquito precautions, especially during the daytime. Application of DEET (N,N-diethyl-m-toluamide) and picaridin-containing agents to the skin or treating clothes with a permethrin-containing agent are just two ways to avoid sustaining a mosquito bite.

While no cases Chikungunya virus have been acquired in the United States, there is a potential risk that the virus will be introduced by an infected traveler or mosquito. The Aedes species that transmits the virus is present in several areas of the United States. For additional information, go to cdc.gov/chikungunya.

Polio. While polio has been eliminated in the United States since 1979, it has never been eradicated in Afghanistan, Nigeria, and Pakistan. For a country to be certified as polio free, there cannot be evidence of circulation of wild polio virus for 3 consecutive years. In spite of a massive global initiative to eliminate this disease, in the last 3 months there have been cases confirmed in the following countries: Cameroon, Ethiopia, Equatorial Guinea, Iraq, Kenya, Somalia, and Syria. While no cases of flaccid paralysis have been confirmed in Israel, wild polio virus has been detected in sewage and isolated from stool of asymptomatic individuals.

Completion of the polio series is recommended for those persons inadequately immunized, and a one-time booster dose is recommended for all adults with travel plans to these countries. This should not be an issue for most pediatric patients, except those who may have deferred immunizations. Booster doses are no longer recommended for travel to countries that border countries with active circulation

African tick bite fever. Frequently overshadowed by the appropriate concern for prevention and acquisition of malaria is a rickettsial disease caused by Rickettsia africae, one of the spotted fever group of rickettsial infections. Its geographic distribution is limited to sub-Saharan Africa, and as its name implies, it is transmitted by a tick. It is the most commonly diagnosed rickettsial disease acquired by travelers (Emerg. Infect. Dis. 2009;15:1791-8). Of 280 individuals diagnosed with rickettsiosis, 231 (82.5%) had spotted fever; almost 87% of the spotted fever rickettsiosis cases were acquired in sub-Saharan Africa, and 69% of these patients reported leisure travel to South Africa. In another review, it was the second-leading cause of systemic febrile illnesses acquired in travelers to sub-Saharan Africa. It was surpassed only by malaria (N. Engl. J. Med. 2006;354:119-30). All age groups are at risk.

Transmission occurs most frequently during the spring and summer months, coinciding with increased tick activity and greater outdoor activities. It is commonly acquired by tourists between November and April in South Africa during a safari or game hunting vacation. Because the incubation period is 5 to 14 days, most travelers may not become symptomatic until after their return. This disease should be suspected in any traveler who presents with fever, headache, and myalgias; has an eschar; and indicates they have recently returned from South Africa. Diagnosis is based on clinical history and serology. Therapy with doxycycline is initiated pending laboratory results.

Disease is controlled by prevention of transmission of the organism by the vector to humans. Use of repellents that contain 20%-30% DEET on exposed skin and wearing clothes treated with permethrin are recommended. Pretreated clothing is also available. Travelers should be encouraged to always check their body after exposure and remove ticks if discovered. Many advocate a bath or shower after coming indoors to facilitate finding any ticks.

Parents should check their children thoroughly for ticks under the arms, in and around the ears, inside the belly button, behind the knees, between the legs, around the waist, and especially in their hair.

 

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She had no relevant financial disclosures. Write to Dr. Word at [email protected].

School’s out for the summer soon! Many of your patients may have plans to travel to areas where they may be exposed to infectious diseases and other health risks not routinely encountered in the United States. They will join the 29 million Americans, including almost 3 million children, who traveled to overseas destinations in 2013. The potential for exposures to these risks is dependent on several factors, including the traveler’s age, health and immunization status, destination, accommodations, and duration of travel. Leisure travel, including visiting friends and relatives, accounts for approximately 90% of overseas travel. Some adolescents are traveling to resource-limited areas for adventure travel, educational experiences, and volunteerism. Many times they will reside with host families as part of this experience. There are also children who will have prolonged stays as a result of parental job relocation.

Unfortunately, health precautions often are not considered as many make their travel arrangements. International trips on average are planned at least 105 days in advance; however, many patients wait until the last minute to seek medical advice, if at all. Of 10,032 ill persons who sought post-travel evaluations at participating surveillance facilities (U.S. GeoSentinel sites) between 1997 and 2011, less than half (44%) reported seeking pretravel advice (MMWR 2013;62(SS03):1-15).

Here are some tips that should be useful and easy to implement in your practice for your internationally traveling patients.

• Make sure routine immunizations are up-to-date for age. The exception to this rule is for measles. All children at least 12 months age should receive two doses of MMR prior to departure regardless of their international destination. The second dose of MMR can be administered as early as 4 weeks after the first. Children between 6 and 11 months of age should receive a single dose of MMR prior to departure. If the initial dose is administered at less than 12 months of age, two additional doses will need to be administered to complete the series beginning at 12 months of age.

While measles is no longer endemic in the United States, as of April 25, 2014, there have been 154 cases reported from 14 states. (See measles graphic.) The majority of cases were imported by unvaccinated travelers who became ill after returning home and exposed susceptible individuals. In the last few years, most of the U.S. cases were imported from Western Europe. Currently, there are several countries experiencing record numbers of cases, including Vietnam (3,700) and the Philippines (26,000). This is not to imply that ongoing international outbreaks are limited to these two countries. For additional information, go to cdc.gov/measles.

• Identify someone in your area as a local resource for travel-related information and referrals. Make sure they are willing to see children. Develop a system to send out reminders to families to seek pretravel advice, ideally at least 1 month prior to departure. For children with chronic diseases or compromised immune systems, destination selection may need to be adjusted depending on their medical needs, availability of comparable health care at the overseas destination, and ability to receive pretravel vaccine interventions. Involvement prior to booking the trip would be advisable. Many offices successfully send out reminders for well visits and influenza vaccine. Consider incorporating one for overseas travel.

• The timing of initiation of antimalarial prophylaxis is dependent on the medication. Weekly medications such as chloroquine and mefloquine should begin at least 2 weeks prior to exposure. Atovaquone/proguanil and doxycycline are two drugs that are administered daily, and travelers can begin as late as 2 days prior to entry into a malaria-endemic area. This is a great option for the last-minute traveler.

However, there are contraindications for the use of each drug. Some are age dependent, while others are directly related to the presence of a specific medical condition. Areas where chloroquine-sensitive malaria is present are limited. It is always important to prescribe a prophylactic antimalarial agent, but even more prudent to prescribe the appropriate drug and dosage.

Not sure which drug is most appropriate for your patient? Refer to your local travel medicine expert, or visit cdc.gov/malaria.

• The accompanying table lists vaccines that are traditionally considered to be travel vaccines, but pediatricians and family physicians might not consider all to belong in that group. Most are not required for entry into a specific country, but are recommended based on the risk for potential exposure and disease acquisition. In contrast, yellow fever and meningococcal vaccines are required for entry into certain countries. Yellow fever vaccine can be administered only at authorized sites and should be received at least 10 days prior to arrival at the destination. As with routinely administered vaccines, occasionally there are shortages of travel-related vaccines. Most recently, a shortage of yellow fever vaccine has been resolved.

 

The majority of vaccines should be administered at least 2 weeks prior to departure, while others, such as rabies and Japanese encephalitis, take at least 28 days to complete the series. These are a few additional reasons it behooves your patients to seek advice early.

Travel updates

Chikungunya virus (CHIK V). Local transmission in the Americas was first reported from St. Martin in December 2013. As of May 5, 2014, a total of 12 Caribbean countries have reported locally acquired cases. The disease is transmitted by Aedes species, which are the same species that transmit dengue fever. Disease is characterized by sudden onset of high fever with severe polyarthralgia. Additional symptoms can include headache, myalgias, rash, nausea, and vomiting. Epidemics have historically occurred in Africa, Asia, and islands in the Indian Ocean. Outbreaks also have occurred in Italy and France.

There is no preventive vaccine or drug available. Treatment is symptomatic care. The disease is best prevented by taking adequate mosquito precautions, especially during the daytime. Application of DEET (N,N-diethyl-m-toluamide) and picaridin-containing agents to the skin or treating clothes with a permethrin-containing agent are just two ways to avoid sustaining a mosquito bite.

While no cases Chikungunya virus have been acquired in the United States, there is a potential risk that the virus will be introduced by an infected traveler or mosquito. The Aedes species that transmits the virus is present in several areas of the United States. For additional information, go to cdc.gov/chikungunya.

Polio. While polio has been eliminated in the United States since 1979, it has never been eradicated in Afghanistan, Nigeria, and Pakistan. For a country to be certified as polio free, there cannot be evidence of circulation of wild polio virus for 3 consecutive years. In spite of a massive global initiative to eliminate this disease, in the last 3 months there have been cases confirmed in the following countries: Cameroon, Ethiopia, Equatorial Guinea, Iraq, Kenya, Somalia, and Syria. While no cases of flaccid paralysis have been confirmed in Israel, wild polio virus has been detected in sewage and isolated from stool of asymptomatic individuals.

Completion of the polio series is recommended for those persons inadequately immunized, and a one-time booster dose is recommended for all adults with travel plans to these countries. This should not be an issue for most pediatric patients, except those who may have deferred immunizations. Booster doses are no longer recommended for travel to countries that border countries with active circulation

African tick bite fever. Frequently overshadowed by the appropriate concern for prevention and acquisition of malaria is a rickettsial disease caused by Rickettsia africae, one of the spotted fever group of rickettsial infections. Its geographic distribution is limited to sub-Saharan Africa, and as its name implies, it is transmitted by a tick. It is the most commonly diagnosed rickettsial disease acquired by travelers (Emerg. Infect. Dis. 2009;15:1791-8). Of 280 individuals diagnosed with rickettsiosis, 231 (82.5%) had spotted fever; almost 87% of the spotted fever rickettsiosis cases were acquired in sub-Saharan Africa, and 69% of these patients reported leisure travel to South Africa. In another review, it was the second-leading cause of systemic febrile illnesses acquired in travelers to sub-Saharan Africa. It was surpassed only by malaria (N. Engl. J. Med. 2006;354:119-30). All age groups are at risk.

Transmission occurs most frequently during the spring and summer months, coinciding with increased tick activity and greater outdoor activities. It is commonly acquired by tourists between November and April in South Africa during a safari or game hunting vacation. Because the incubation period is 5 to 14 days, most travelers may not become symptomatic until after their return. This disease should be suspected in any traveler who presents with fever, headache, and myalgias; has an eschar; and indicates they have recently returned from South Africa. Diagnosis is based on clinical history and serology. Therapy with doxycycline is initiated pending laboratory results.

Disease is controlled by prevention of transmission of the organism by the vector to humans. Use of repellents that contain 20%-30% DEET on exposed skin and wearing clothes treated with permethrin are recommended. Pretreated clothing is also available. Travelers should be encouraged to always check their body after exposure and remove ticks if discovered. Many advocate a bath or shower after coming indoors to facilitate finding any ticks.

Parents should check their children thoroughly for ticks under the arms, in and around the ears, inside the belly button, behind the knees, between the legs, around the waist, and especially in their hair.

 

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She had no relevant financial disclosures. Write to Dr. Word at [email protected].

School’s out for the summer soon! Many of your patients may have plans to travel to areas where they may be exposed to infectious diseases and other health risks not routinely encountered in the United States. They will join the 29 million Americans, including almost 3 million children, who traveled to overseas destinations in 2013. The potential for exposures to these risks is dependent on several factors, including the traveler’s age, health and immunization status, destination, accommodations, and duration of travel. Leisure travel, including visiting friends and relatives, accounts for approximately 90% of overseas travel. Some adolescents are traveling to resource-limited areas for adventure travel, educational experiences, and volunteerism. Many times they will reside with host families as part of this experience. There are also children who will have prolonged stays as a result of parental job relocation.

Unfortunately, health precautions often are not considered as many make their travel arrangements. International trips on average are planned at least 105 days in advance; however, many patients wait until the last minute to seek medical advice, if at all. Of 10,032 ill persons who sought post-travel evaluations at participating surveillance facilities (U.S. GeoSentinel sites) between 1997 and 2011, less than half (44%) reported seeking pretravel advice (MMWR 2013;62(SS03):1-15).

Here are some tips that should be useful and easy to implement in your practice for your internationally traveling patients.

• Make sure routine immunizations are up-to-date for age. The exception to this rule is for measles. All children at least 12 months age should receive two doses of MMR prior to departure regardless of their international destination. The second dose of MMR can be administered as early as 4 weeks after the first. Children between 6 and 11 months of age should receive a single dose of MMR prior to departure. If the initial dose is administered at less than 12 months of age, two additional doses will need to be administered to complete the series beginning at 12 months of age.

While measles is no longer endemic in the United States, as of April 25, 2014, there have been 154 cases reported from 14 states. (See measles graphic.) The majority of cases were imported by unvaccinated travelers who became ill after returning home and exposed susceptible individuals. In the last few years, most of the U.S. cases were imported from Western Europe. Currently, there are several countries experiencing record numbers of cases, including Vietnam (3,700) and the Philippines (26,000). This is not to imply that ongoing international outbreaks are limited to these two countries. For additional information, go to cdc.gov/measles.

• Identify someone in your area as a local resource for travel-related information and referrals. Make sure they are willing to see children. Develop a system to send out reminders to families to seek pretravel advice, ideally at least 1 month prior to departure. For children with chronic diseases or compromised immune systems, destination selection may need to be adjusted depending on their medical needs, availability of comparable health care at the overseas destination, and ability to receive pretravel vaccine interventions. Involvement prior to booking the trip would be advisable. Many offices successfully send out reminders for well visits and influenza vaccine. Consider incorporating one for overseas travel.

• The timing of initiation of antimalarial prophylaxis is dependent on the medication. Weekly medications such as chloroquine and mefloquine should begin at least 2 weeks prior to exposure. Atovaquone/proguanil and doxycycline are two drugs that are administered daily, and travelers can begin as late as 2 days prior to entry into a malaria-endemic area. This is a great option for the last-minute traveler.

However, there are contraindications for the use of each drug. Some are age dependent, while others are directly related to the presence of a specific medical condition. Areas where chloroquine-sensitive malaria is present are limited. It is always important to prescribe a prophylactic antimalarial agent, but even more prudent to prescribe the appropriate drug and dosage.

Not sure which drug is most appropriate for your patient? Refer to your local travel medicine expert, or visit cdc.gov/malaria.

• The accompanying table lists vaccines that are traditionally considered to be travel vaccines, but pediatricians and family physicians might not consider all to belong in that group. Most are not required for entry into a specific country, but are recommended based on the risk for potential exposure and disease acquisition. In contrast, yellow fever and meningococcal vaccines are required for entry into certain countries. Yellow fever vaccine can be administered only at authorized sites and should be received at least 10 days prior to arrival at the destination. As with routinely administered vaccines, occasionally there are shortages of travel-related vaccines. Most recently, a shortage of yellow fever vaccine has been resolved.

 

The majority of vaccines should be administered at least 2 weeks prior to departure, while others, such as rabies and Japanese encephalitis, take at least 28 days to complete the series. These are a few additional reasons it behooves your patients to seek advice early.

Travel updates

Chikungunya virus (CHIK V). Local transmission in the Americas was first reported from St. Martin in December 2013. As of May 5, 2014, a total of 12 Caribbean countries have reported locally acquired cases. The disease is transmitted by Aedes species, which are the same species that transmit dengue fever. Disease is characterized by sudden onset of high fever with severe polyarthralgia. Additional symptoms can include headache, myalgias, rash, nausea, and vomiting. Epidemics have historically occurred in Africa, Asia, and islands in the Indian Ocean. Outbreaks also have occurred in Italy and France.

There is no preventive vaccine or drug available. Treatment is symptomatic care. The disease is best prevented by taking adequate mosquito precautions, especially during the daytime. Application of DEET (N,N-diethyl-m-toluamide) and picaridin-containing agents to the skin or treating clothes with a permethrin-containing agent are just two ways to avoid sustaining a mosquito bite.

While no cases Chikungunya virus have been acquired in the United States, there is a potential risk that the virus will be introduced by an infected traveler or mosquito. The Aedes species that transmits the virus is present in several areas of the United States. For additional information, go to cdc.gov/chikungunya.

Polio. While polio has been eliminated in the United States since 1979, it has never been eradicated in Afghanistan, Nigeria, and Pakistan. For a country to be certified as polio free, there cannot be evidence of circulation of wild polio virus for 3 consecutive years. In spite of a massive global initiative to eliminate this disease, in the last 3 months there have been cases confirmed in the following countries: Cameroon, Ethiopia, Equatorial Guinea, Iraq, Kenya, Somalia, and Syria. While no cases of flaccid paralysis have been confirmed in Israel, wild polio virus has been detected in sewage and isolated from stool of asymptomatic individuals.

Completion of the polio series is recommended for those persons inadequately immunized, and a one-time booster dose is recommended for all adults with travel plans to these countries. This should not be an issue for most pediatric patients, except those who may have deferred immunizations. Booster doses are no longer recommended for travel to countries that border countries with active circulation

African tick bite fever. Frequently overshadowed by the appropriate concern for prevention and acquisition of malaria is a rickettsial disease caused by Rickettsia africae, one of the spotted fever group of rickettsial infections. Its geographic distribution is limited to sub-Saharan Africa, and as its name implies, it is transmitted by a tick. It is the most commonly diagnosed rickettsial disease acquired by travelers (Emerg. Infect. Dis. 2009;15:1791-8). Of 280 individuals diagnosed with rickettsiosis, 231 (82.5%) had spotted fever; almost 87% of the spotted fever rickettsiosis cases were acquired in sub-Saharan Africa, and 69% of these patients reported leisure travel to South Africa. In another review, it was the second-leading cause of systemic febrile illnesses acquired in travelers to sub-Saharan Africa. It was surpassed only by malaria (N. Engl. J. Med. 2006;354:119-30). All age groups are at risk.

Transmission occurs most frequently during the spring and summer months, coinciding with increased tick activity and greater outdoor activities. It is commonly acquired by tourists between November and April in South Africa during a safari or game hunting vacation. Because the incubation period is 5 to 14 days, most travelers may not become symptomatic until after their return. This disease should be suspected in any traveler who presents with fever, headache, and myalgias; has an eschar; and indicates they have recently returned from South Africa. Diagnosis is based on clinical history and serology. Therapy with doxycycline is initiated pending laboratory results.

Disease is controlled by prevention of transmission of the organism by the vector to humans. Use of repellents that contain 20%-30% DEET on exposed skin and wearing clothes treated with permethrin are recommended. Pretreated clothing is also available. Travelers should be encouraged to always check their body after exposure and remove ticks if discovered. Many advocate a bath or shower after coming indoors to facilitate finding any ticks.

Parents should check their children thoroughly for ticks under the arms, in and around the ears, inside the belly button, behind the knees, between the legs, around the waist, and especially in their hair.

 

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She had no relevant financial disclosures. Write to Dr. Word at [email protected].

The true prevalence and meaning of Clostridium difficile detection in children remains an issue despite a known high prevalence of asymptomatic colonization in children during the first 3 years of life. Distinguishing C. difficile disease from colonization is difficult. Endoscopy can identify some severe C. difficile disease, but what about mild to moderate C. difficile infection?

A passive Centers for Disease Control and Prevention surveillance study (Pediatrics 2014;133:651-8) helps in understanding C. difficile prevalence by documenting the relatively high prevalence of community-acquired C. difficile often associated with use of common oral antibiotics and possibly because of the emergence of the NAP1 strain, which is also emerging in adults. But distinguishing infection from colonization remains an issue. The data have implications for everyday pediatric care.

Methods

Children aged 1-17 years from 10 U.S. states were studied during 2011-2012. C. difficile "cases" were defined via a positive toxin or a molecular test ordered as part of standard care. Standard of care testing for other selected gastrointestinal pathogens and data from medical records were collected. Within 3-6 months of the C. difficile–positive test, a convenience sample of families (about 9%) underwent a telephone interview.

Factors in C. difficile detection

C. difficile was detected in 944 stools from 885 children with no gender difference. The highest rates per 100,000 by race were in whites (23.9) vs. nonwhites (17.4), and in 12- to 23-month-olds (66.3). Overall, 71% of detections were categorized from charted data as community acquired. Only 17% were associated with outpatient health care and 12% with inpatient care.

Antibiotic use in the 14 days before a C. difficile–positive stool was 33% among all cases with no age group differences. Cephalosporins (41%) and amoxicillin/clavulanate (28%) were most common. Among 84 cases also later interviewed by phone, antibiotic use was more frequent (73%); penicillins (39%) and cephalosporins (44%) were the antibiotics most commonly used in this subset of patients. Indications were most often otitis, sinusitis, or upper respiratory infection. In the phone interviews, outpatient office visits were a more frequent (97%) health care exposure than in the overall case population.

Signs and symptoms were mild and similar in all age groups. Diarrhea was not present in 28%. Coinfection with another enteric pathogen was identified in 3% of 535 tested samples: bacterial (n = 12), protozoal (n = 4), and viral (n = 1) – and more common in 2- to 9-year-olds (P = .03). Peripheral WBC counts were abnormal (greater than 15, 000/mm³) in only 7%. There was radiographic evidence of ileus in three and pseudomembranous colitis developed in five cases. Cases were defined as severe in 8% with no age preponderance. There were no deaths.

Infection vs. colonization?

The authors reason that similar clinical presentations and symptom severity at all ages means that detection of C. difficile "likely represents infection" but not colonization. They explain that they expect milder symptoms in the youngest cases if they were only colonized. Is this reasonable?

One could counterargue that in the absence of testing for the most common diarrheagenic pathogen in the United States (norovirus), that diarrhea in at least some of these C. difficile–positive children was likely caused by undetected norovirus. That could partially explain why symptoms were not significantly different by age. One viral coinfection in nearly 500 diarrhea stools (even preselected by C. difficile positivity) seems low. Even if norovirus is not the wildcard here, the similar "disease" at all ages could suggest that something other than C. difficile is the cause. Norovirus and other viral agents testing of samples that were cultured for C. difficile could increase understanding of coinfection rates. Another issue is that 28% of C. difficile children did not have diarrhea, raising concern that these were colonized children.

The authors state that high antibiotic use (73% in phone interviewees) might have contributed to the high C. difficile detection rates. This seems logical, but the phone-derived data came from only about 8% of the total population. The original charted data from the entire population showed 33% antibiotic use. The charted data may have been more reliable because it was collected at the time of the C. difficile–positive stool, not 3-6 months later. Nevertheless, it seems apparent that common outpatient antibiotics could be a factor. If the data were compared with antibiotic use rates for C. difficile–negative children of the same ages, the conclusion would be more powerful.

Children less than 1year of age were not included because up to 73% (Eur. J. Clin. Microbiol. Infect. Dis. 1989;8:390-3) of infants have been reported as asymptomatically colonized. In similar studies, colonized infants were frequent (25% between 6 days and 6 months) up to about 3 years of age when rates dropped off to less than 3%, similar to adults. Inclusion of children in the second and third year of life likely means that not all detections were infections. But there is no way to definitively distinguish infection from colonization in this study.

 

A further step in filling the knowledge gap on C. difficile would be prospective surveillance with improved definitions of infection vs. colonization and a more complete search for potential concurrent causes of diarrhea. Undoubtedly, many of these C. difficile–positive children had true infection, but it also seems likely that some were colonized, particularly in the second and third year of life. It would be interesting to compare results from healthy controls vs. those with diarrhea using new multiplex molecular assays to gain a better understanding of what proportion of all children have detectable C. difficile with and without other pathogens.

Bottom line

NAP1 C. difficile is emerging in children. C. difficile detection, whether infected or colonized, in this many children is new. These data suggest that our best contributions to reducing the spread of C. difficile are the use of amoxicillin without clavulanate as first line – if antibiotics are needed for acute otitis media and for acute sinusitis – while we refrain from antibiotics for viral upper respiratory infections. As the old knight told Indiana Jones, "Choose wisely."

Factors associated with C. difficile detection in children

1. White race. Question more frequent health care and antibiotic exposure.

2. Age 12 to 23 months. Question whether the population is mix of colonized and infected children. This needs more study.

3. Amoxicillin/clavulanate or oral cephalosporin use for common outpatient infection. Is narrower spectrum, amoxicillin alone better?

4. A recent outpatient health care visit may be a cofactor with #1 and #3.

Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. Dr. Harrison said he has no relevant financial disclosures. E-mail him at [email protected].

The true prevalence and meaning of Clostridium difficile detection in children remains an issue despite a known high prevalence of asymptomatic colonization in children during the first 3 years of life. Distinguishing C. difficile disease from colonization is difficult. Endoscopy can identify some severe C. difficile disease, but what about mild to moderate C. difficile infection?

A passive Centers for Disease Control and Prevention surveillance study (Pediatrics 2014;133:651-8) helps in understanding C. difficile prevalence by documenting the relatively high prevalence of community-acquired C. difficile often associated with use of common oral antibiotics and possibly because of the emergence of the NAP1 strain, which is also emerging in adults. But distinguishing infection from colonization remains an issue. The data have implications for everyday pediatric care.

Methods

Children aged 1-17 years from 10 U.S. states were studied during 2011-2012. C. difficile "cases" were defined via a positive toxin or a molecular test ordered as part of standard care. Standard of care testing for other selected gastrointestinal pathogens and data from medical records were collected. Within 3-6 months of the C. difficile–positive test, a convenience sample of families (about 9%) underwent a telephone interview.

Factors in C. difficile detection

C. difficile was detected in 944 stools from 885 children with no gender difference. The highest rates per 100,000 by race were in whites (23.9) vs. nonwhites (17.4), and in 12- to 23-month-olds (66.3). Overall, 71% of detections were categorized from charted data as community acquired. Only 17% were associated with outpatient health care and 12% with inpatient care.

Antibiotic use in the 14 days before a C. difficile–positive stool was 33% among all cases with no age group differences. Cephalosporins (41%) and amoxicillin/clavulanate (28%) were most common. Among 84 cases also later interviewed by phone, antibiotic use was more frequent (73%); penicillins (39%) and cephalosporins (44%) were the antibiotics most commonly used in this subset of patients. Indications were most often otitis, sinusitis, or upper respiratory infection. In the phone interviews, outpatient office visits were a more frequent (97%) health care exposure than in the overall case population.

Signs and symptoms were mild and similar in all age groups. Diarrhea was not present in 28%. Coinfection with another enteric pathogen was identified in 3% of 535 tested samples: bacterial (n = 12), protozoal (n = 4), and viral (n = 1) – and more common in 2- to 9-year-olds (P = .03). Peripheral WBC counts were abnormal (greater than 15, 000/mm³) in only 7%. There was radiographic evidence of ileus in three and pseudomembranous colitis developed in five cases. Cases were defined as severe in 8% with no age preponderance. There were no deaths.

Infection vs. colonization?

The authors reason that similar clinical presentations and symptom severity at all ages means that detection of C. difficile "likely represents infection" but not colonization. They explain that they expect milder symptoms in the youngest cases if they were only colonized. Is this reasonable?

One could counterargue that in the absence of testing for the most common diarrheagenic pathogen in the United States (norovirus), that diarrhea in at least some of these C. difficile–positive children was likely caused by undetected norovirus. That could partially explain why symptoms were not significantly different by age. One viral coinfection in nearly 500 diarrhea stools (even preselected by C. difficile positivity) seems low. Even if norovirus is not the wildcard here, the similar "disease" at all ages could suggest that something other than C. difficile is the cause. Norovirus and other viral agents testing of samples that were cultured for C. difficile could increase understanding of coinfection rates. Another issue is that 28% of C. difficile children did not have diarrhea, raising concern that these were colonized children.

The authors state that high antibiotic use (73% in phone interviewees) might have contributed to the high C. difficile detection rates. This seems logical, but the phone-derived data came from only about 8% of the total population. The original charted data from the entire population showed 33% antibiotic use. The charted data may have been more reliable because it was collected at the time of the C. difficile–positive stool, not 3-6 months later. Nevertheless, it seems apparent that common outpatient antibiotics could be a factor. If the data were compared with antibiotic use rates for C. difficile–negative children of the same ages, the conclusion would be more powerful.

Children less than 1year of age were not included because up to 73% (Eur. J. Clin. Microbiol. Infect. Dis. 1989;8:390-3) of infants have been reported as asymptomatically colonized. In similar studies, colonized infants were frequent (25% between 6 days and 6 months) up to about 3 years of age when rates dropped off to less than 3%, similar to adults. Inclusion of children in the second and third year of life likely means that not all detections were infections. But there is no way to definitively distinguish infection from colonization in this study.

 

A further step in filling the knowledge gap on C. difficile would be prospective surveillance with improved definitions of infection vs. colonization and a more complete search for potential concurrent causes of diarrhea. Undoubtedly, many of these C. difficile–positive children had true infection, but it also seems likely that some were colonized, particularly in the second and third year of life. It would be interesting to compare results from healthy controls vs. those with diarrhea using new multiplex molecular assays to gain a better understanding of what proportion of all children have detectable C. difficile with and without other pathogens.

Bottom line

NAP1 C. difficile is emerging in children. C. difficile detection, whether infected or colonized, in this many children is new. These data suggest that our best contributions to reducing the spread of C. difficile are the use of amoxicillin without clavulanate as first line – if antibiotics are needed for acute otitis media and for acute sinusitis – while we refrain from antibiotics for viral upper respiratory infections. As the old knight told Indiana Jones, "Choose wisely."

Factors associated with C. difficile detection in children

1. White race. Question more frequent health care and antibiotic exposure.

2. Age 12 to 23 months. Question whether the population is mix of colonized and infected children. This needs more study.

3. Amoxicillin/clavulanate or oral cephalosporin use for common outpatient infection. Is narrower spectrum, amoxicillin alone better?

4. A recent outpatient health care visit may be a cofactor with #1 and #3.

Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. Dr. Harrison said he has no relevant financial disclosures. E-mail him at [email protected].

The true prevalence and meaning of Clostridium difficile detection in children remains an issue despite a known high prevalence of asymptomatic colonization in children during the first 3 years of life. Distinguishing C. difficile disease from colonization is difficult. Endoscopy can identify some severe C. difficile disease, but what about mild to moderate C. difficile infection?

A passive Centers for Disease Control and Prevention surveillance study (Pediatrics 2014;133:651-8) helps in understanding C. difficile prevalence by documenting the relatively high prevalence of community-acquired C. difficile often associated with use of common oral antibiotics and possibly because of the emergence of the NAP1 strain, which is also emerging in adults. But distinguishing infection from colonization remains an issue. The data have implications for everyday pediatric care.

Methods

Children aged 1-17 years from 10 U.S. states were studied during 2011-2012. C. difficile "cases" were defined via a positive toxin or a molecular test ordered as part of standard care. Standard of care testing for other selected gastrointestinal pathogens and data from medical records were collected. Within 3-6 months of the C. difficile–positive test, a convenience sample of families (about 9%) underwent a telephone interview.

Factors in C. difficile detection

C. difficile was detected in 944 stools from 885 children with no gender difference. The highest rates per 100,000 by race were in whites (23.9) vs. nonwhites (17.4), and in 12- to 23-month-olds (66.3). Overall, 71% of detections were categorized from charted data as community acquired. Only 17% were associated with outpatient health care and 12% with inpatient care.

Antibiotic use in the 14 days before a C. difficile–positive stool was 33% among all cases with no age group differences. Cephalosporins (41%) and amoxicillin/clavulanate (28%) were most common. Among 84 cases also later interviewed by phone, antibiotic use was more frequent (73%); penicillins (39%) and cephalosporins (44%) were the antibiotics most commonly used in this subset of patients. Indications were most often otitis, sinusitis, or upper respiratory infection. In the phone interviews, outpatient office visits were a more frequent (97%) health care exposure than in the overall case population.

Signs and symptoms were mild and similar in all age groups. Diarrhea was not present in 28%. Coinfection with another enteric pathogen was identified in 3% of 535 tested samples: bacterial (n = 12), protozoal (n = 4), and viral (n = 1) – and more common in 2- to 9-year-olds (P = .03). Peripheral WBC counts were abnormal (greater than 15, 000/mm³) in only 7%. There was radiographic evidence of ileus in three and pseudomembranous colitis developed in five cases. Cases were defined as severe in 8% with no age preponderance. There were no deaths.

Infection vs. colonization?

The authors reason that similar clinical presentations and symptom severity at all ages means that detection of C. difficile "likely represents infection" but not colonization. They explain that they expect milder symptoms in the youngest cases if they were only colonized. Is this reasonable?

One could counterargue that in the absence of testing for the most common diarrheagenic pathogen in the United States (norovirus), that diarrhea in at least some of these C. difficile–positive children was likely caused by undetected norovirus. That could partially explain why symptoms were not significantly different by age. One viral coinfection in nearly 500 diarrhea stools (even preselected by C. difficile positivity) seems low. Even if norovirus is not the wildcard here, the similar "disease" at all ages could suggest that something other than C. difficile is the cause. Norovirus and other viral agents testing of samples that were cultured for C. difficile could increase understanding of coinfection rates. Another issue is that 28% of C. difficile children did not have diarrhea, raising concern that these were colonized children.

The authors state that high antibiotic use (73% in phone interviewees) might have contributed to the high C. difficile detection rates. This seems logical, but the phone-derived data came from only about 8% of the total population. The original charted data from the entire population showed 33% antibiotic use. The charted data may have been more reliable because it was collected at the time of the C. difficile–positive stool, not 3-6 months later. Nevertheless, it seems apparent that common outpatient antibiotics could be a factor. If the data were compared with antibiotic use rates for C. difficile–negative children of the same ages, the conclusion would be more powerful.

Children less than 1year of age were not included because up to 73% (Eur. J. Clin. Microbiol. Infect. Dis. 1989;8:390-3) of infants have been reported as asymptomatically colonized. In similar studies, colonized infants were frequent (25% between 6 days and 6 months) up to about 3 years of age when rates dropped off to less than 3%, similar to adults. Inclusion of children in the second and third year of life likely means that not all detections were infections. But there is no way to definitively distinguish infection from colonization in this study.

 

A further step in filling the knowledge gap on C. difficile would be prospective surveillance with improved definitions of infection vs. colonization and a more complete search for potential concurrent causes of diarrhea. Undoubtedly, many of these C. difficile–positive children had true infection, but it also seems likely that some were colonized, particularly in the second and third year of life. It would be interesting to compare results from healthy controls vs. those with diarrhea using new multiplex molecular assays to gain a better understanding of what proportion of all children have detectable C. difficile with and without other pathogens.

Bottom line

NAP1 C. difficile is emerging in children. C. difficile detection, whether infected or colonized, in this many children is new. These data suggest that our best contributions to reducing the spread of C. difficile are the use of amoxicillin without clavulanate as first line – if antibiotics are needed for acute otitis media and for acute sinusitis – while we refrain from antibiotics for viral upper respiratory infections. As the old knight told Indiana Jones, "Choose wisely."

Factors associated with C. difficile detection in children

1. White race. Question more frequent health care and antibiotic exposure.

2. Age 12 to 23 months. Question whether the population is mix of colonized and infected children. This needs more study.

3. Amoxicillin/clavulanate or oral cephalosporin use for common outpatient infection. Is narrower spectrum, amoxicillin alone better?

4. A recent outpatient health care visit may be a cofactor with #1 and #3.

Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. Dr. Harrison said he has no relevant financial disclosures. E-mail him at [email protected].

Febrile neonates represent a challenge to clinicians as the risk for serious bacterial infections is highest at this age, the presence of discriminating clinical signs are often absent, and outcomes can be poor in the absence of early treatment. For this reason, most experts recommend that all neonates with a rectal temperature 38°C or higher have blood, urine, and cerebrospinal fluid cultures regardless of clinical appearance (Ann. Emerg. Med. 1993;22:1198-1210). Such neonates should be admitted to the hospital and treated with empiric antibiotics.

In a study of 41,890 neonates (up to 28 days of age) evaluated in 36 pediatric emergency departments, 2,253 (5.4%) were febrile. Three hundred sixty-nine (16%) infants were seen, then discharged from the ED; the remaining 1,884 (84%) were seen and admitted.

As with prior studies, a high rate of serious infection (12%) was documented; urinary tract infection (27%), meningitis (19%), bacteremia and sepsis (14%), cellulitis and soft tissue infections (6%), and pneumonia (3%) were most common. Of the 369 infants discharged, 3 (1%) had serious infection; of the 1,884 admitted, 266 (14%) did.

The study demonstrated significant variability in the approach used to evaluate and treat febrile neonates, with 16% of infants being discharged from the emergency department, the majority of whom (97%) did not get antimicrobial therapy. Sixty-four (3%) of all febrile infants were discharged without any laboratory evaluation or treatment. Eighty-four percent of febrile infants were admitted to the hospital, and 96% of those admitted received antimicrobial treatment (Pediatrics 2014;133:187).

Prior studies reported that serious bacterial infection was uncommon in febrile neonates who met the following six low-risk criteria: 1. an unremarkable medical history, 2. a healthy, nontoxic appearance, 3. no focal signs of infection, 4. an erythrocyte sedimentation rate less than 30 mm at the end of the first hour, 5. a white blood cell count of 5,000-15,000/mcL, and 6. a normal urine analysis (Arch. Dis. Child Fetal Neonatal Ed. 2007;92:F15-8).

Although it is unclear what criteria were used to discharge febrile neonates from the pediatric ED in the current study, only 1 of the 369 neonates discharged from the pediatric ED subsequently returned to the same pediatric ED and was diagnosed with serious infection; however, only 10 in total returned for evaluation. How many subsequently were diagnosed with serious infection at a different facility is unknown. These results were consistent with the initial studies of the "low-risk criteria," which indicates these criteria are not sufficiently reliable to exclude the presence of serious infection.

The study demonstrates that there remains disagreement about how febrile neonates should be evaluated and managed in the ED setting, and how much reliance should be placed on clinical and laboratory parameters. Unlike children older than 3 months of age, in whom immunization with Haemophilus influenzae type b and 13-valent pneumococcal conjugate vaccines has dramatically reduced the incidence of invasive disease, serious infection in febrile neonates up to 28 days of age remains common.

The current spectrum of pathogens and disease – gram-negative uropathogens, staphylococcal and streptococcal skin and soft tissue infections, group B Streptococcus and Staphylococcus aureus bacteremia, and CNS infection – have not been significantly impacted by efforts to prevent "early-onset" neonatal sepsis and by vaccine strategies that target primarily older children. Age remains a risk, with a decreasing incidence of serious bacterial infection as each week of life passes. However, in another study, the rate of serious bacterial infection in febrile neonates 15-21 days of age was found to be sufficiently high to warrant comparable management to that given younger neonates (Pediatr. Inf. Dis. J. 2012;31:455-8).

Thus, currently there seem to be few strategies that would protect febrile neonates from delays in therapy and preventable outcomes, other than the traditional practice of thorough medical evaluation, laboratory testing to include blood, urine, and cerebrospinal fluid cultures, chest x-ray when respiratory tract signs/symptoms are present, and presumptive treatment with parenteral antibiotic therapy.

Office-based studies report greater reliance on clinical judgment with the belief that reliance on clinical guidelines would have only a small benefit, if any, but would result in greater hospitalization and laboratory testing (JAMA 2004;291:1203-12). Still the high rate of disease (14%) in those admitted to the hospital underscore the vulnerability of this age group, the significance of fever, and the potential for a poor outcome without thorough evaluation of each child and presumptive treatment for serious bacterial infection.

Dr. Pelton is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. Dr. Pelton said he had no relevant financial disclosures. E-mail him at [email protected].

Febrile neonates represent a challenge to clinicians as the risk for serious bacterial infections is highest at this age, the presence of discriminating clinical signs are often absent, and outcomes can be poor in the absence of early treatment. For this reason, most experts recommend that all neonates with a rectal temperature 38°C or higher have blood, urine, and cerebrospinal fluid cultures regardless of clinical appearance (Ann. Emerg. Med. 1993;22:1198-1210). Such neonates should be admitted to the hospital and treated with empiric antibiotics.

In a study of 41,890 neonates (up to 28 days of age) evaluated in 36 pediatric emergency departments, 2,253 (5.4%) were febrile. Three hundred sixty-nine (16%) infants were seen, then discharged from the ED; the remaining 1,884 (84%) were seen and admitted.

As with prior studies, a high rate of serious infection (12%) was documented; urinary tract infection (27%), meningitis (19%), bacteremia and sepsis (14%), cellulitis and soft tissue infections (6%), and pneumonia (3%) were most common. Of the 369 infants discharged, 3 (1%) had serious infection; of the 1,884 admitted, 266 (14%) did.

The study demonstrated significant variability in the approach used to evaluate and treat febrile neonates, with 16% of infants being discharged from the emergency department, the majority of whom (97%) did not get antimicrobial therapy. Sixty-four (3%) of all febrile infants were discharged without any laboratory evaluation or treatment. Eighty-four percent of febrile infants were admitted to the hospital, and 96% of those admitted received antimicrobial treatment (Pediatrics 2014;133:187).

Prior studies reported that serious bacterial infection was uncommon in febrile neonates who met the following six low-risk criteria: 1. an unremarkable medical history, 2. a healthy, nontoxic appearance, 3. no focal signs of infection, 4. an erythrocyte sedimentation rate less than 30 mm at the end of the first hour, 5. a white blood cell count of 5,000-15,000/mcL, and 6. a normal urine analysis (Arch. Dis. Child Fetal Neonatal Ed. 2007;92:F15-8).

Although it is unclear what criteria were used to discharge febrile neonates from the pediatric ED in the current study, only 1 of the 369 neonates discharged from the pediatric ED subsequently returned to the same pediatric ED and was diagnosed with serious infection; however, only 10 in total returned for evaluation. How many subsequently were diagnosed with serious infection at a different facility is unknown. These results were consistent with the initial studies of the "low-risk criteria," which indicates these criteria are not sufficiently reliable to exclude the presence of serious infection.

The study demonstrates that there remains disagreement about how febrile neonates should be evaluated and managed in the ED setting, and how much reliance should be placed on clinical and laboratory parameters. Unlike children older than 3 months of age, in whom immunization with Haemophilus influenzae type b and 13-valent pneumococcal conjugate vaccines has dramatically reduced the incidence of invasive disease, serious infection in febrile neonates up to 28 days of age remains common.

The current spectrum of pathogens and disease – gram-negative uropathogens, staphylococcal and streptococcal skin and soft tissue infections, group B Streptococcus and Staphylococcus aureus bacteremia, and CNS infection – have not been significantly impacted by efforts to prevent "early-onset" neonatal sepsis and by vaccine strategies that target primarily older children. Age remains a risk, with a decreasing incidence of serious bacterial infection as each week of life passes. However, in another study, the rate of serious bacterial infection in febrile neonates 15-21 days of age was found to be sufficiently high to warrant comparable management to that given younger neonates (Pediatr. Inf. Dis. J. 2012;31:455-8).

Thus, currently there seem to be few strategies that would protect febrile neonates from delays in therapy and preventable outcomes, other than the traditional practice of thorough medical evaluation, laboratory testing to include blood, urine, and cerebrospinal fluid cultures, chest x-ray when respiratory tract signs/symptoms are present, and presumptive treatment with parenteral antibiotic therapy.

Office-based studies report greater reliance on clinical judgment with the belief that reliance on clinical guidelines would have only a small benefit, if any, but would result in greater hospitalization and laboratory testing (JAMA 2004;291:1203-12). Still the high rate of disease (14%) in those admitted to the hospital underscore the vulnerability of this age group, the significance of fever, and the potential for a poor outcome without thorough evaluation of each child and presumptive treatment for serious bacterial infection.

Dr. Pelton is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. Dr. Pelton said he had no relevant financial disclosures. E-mail him at [email protected].

Febrile neonates represent a challenge to clinicians as the risk for serious bacterial infections is highest at this age, the presence of discriminating clinical signs are often absent, and outcomes can be poor in the absence of early treatment. For this reason, most experts recommend that all neonates with a rectal temperature 38°C or higher have blood, urine, and cerebrospinal fluid cultures regardless of clinical appearance (Ann. Emerg. Med. 1993;22:1198-1210). Such neonates should be admitted to the hospital and treated with empiric antibiotics.

In a study of 41,890 neonates (up to 28 days of age) evaluated in 36 pediatric emergency departments, 2,253 (5.4%) were febrile. Three hundred sixty-nine (16%) infants were seen, then discharged from the ED; the remaining 1,884 (84%) were seen and admitted.

As with prior studies, a high rate of serious infection (12%) was documented; urinary tract infection (27%), meningitis (19%), bacteremia and sepsis (14%), cellulitis and soft tissue infections (6%), and pneumonia (3%) were most common. Of the 369 infants discharged, 3 (1%) had serious infection; of the 1,884 admitted, 266 (14%) did.

The study demonstrated significant variability in the approach used to evaluate and treat febrile neonates, with 16% of infants being discharged from the emergency department, the majority of whom (97%) did not get antimicrobial therapy. Sixty-four (3%) of all febrile infants were discharged without any laboratory evaluation or treatment. Eighty-four percent of febrile infants were admitted to the hospital, and 96% of those admitted received antimicrobial treatment (Pediatrics 2014;133:187).

Prior studies reported that serious bacterial infection was uncommon in febrile neonates who met the following six low-risk criteria: 1. an unremarkable medical history, 2. a healthy, nontoxic appearance, 3. no focal signs of infection, 4. an erythrocyte sedimentation rate less than 30 mm at the end of the first hour, 5. a white blood cell count of 5,000-15,000/mcL, and 6. a normal urine analysis (Arch. Dis. Child Fetal Neonatal Ed. 2007;92:F15-8).

Although it is unclear what criteria were used to discharge febrile neonates from the pediatric ED in the current study, only 1 of the 369 neonates discharged from the pediatric ED subsequently returned to the same pediatric ED and was diagnosed with serious infection; however, only 10 in total returned for evaluation. How many subsequently were diagnosed with serious infection at a different facility is unknown. These results were consistent with the initial studies of the "low-risk criteria," which indicates these criteria are not sufficiently reliable to exclude the presence of serious infection.

The study demonstrates that there remains disagreement about how febrile neonates should be evaluated and managed in the ED setting, and how much reliance should be placed on clinical and laboratory parameters. Unlike children older than 3 months of age, in whom immunization with Haemophilus influenzae type b and 13-valent pneumococcal conjugate vaccines has dramatically reduced the incidence of invasive disease, serious infection in febrile neonates up to 28 days of age remains common.

The current spectrum of pathogens and disease – gram-negative uropathogens, staphylococcal and streptococcal skin and soft tissue infections, group B Streptococcus and Staphylococcus aureus bacteremia, and CNS infection – have not been significantly impacted by efforts to prevent "early-onset" neonatal sepsis and by vaccine strategies that target primarily older children. Age remains a risk, with a decreasing incidence of serious bacterial infection as each week of life passes. However, in another study, the rate of serious bacterial infection in febrile neonates 15-21 days of age was found to be sufficiently high to warrant comparable management to that given younger neonates (Pediatr. Inf. Dis. J. 2012;31:455-8).

Thus, currently there seem to be few strategies that would protect febrile neonates from delays in therapy and preventable outcomes, other than the traditional practice of thorough medical evaluation, laboratory testing to include blood, urine, and cerebrospinal fluid cultures, chest x-ray when respiratory tract signs/symptoms are present, and presumptive treatment with parenteral antibiotic therapy.

Office-based studies report greater reliance on clinical judgment with the belief that reliance on clinical guidelines would have only a small benefit, if any, but would result in greater hospitalization and laboratory testing (JAMA 2004;291:1203-12). Still the high rate of disease (14%) in those admitted to the hospital underscore the vulnerability of this age group, the significance of fever, and the potential for a poor outcome without thorough evaluation of each child and presumptive treatment for serious bacterial infection.

Dr. Pelton is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. Dr. Pelton said he had no relevant financial disclosures. E-mail him at [email protected].

The U.S. immunization program has been one of the country’s most successful initiatives and best investments. Prior to 2005, vaccines were targeted for administration to infants and young children. Adolescence was a period for catch-up immunizations. All that changed in 2005 when the first meningococcal conjugate vaccine (MCV) was recommended for administration to preteens at 11-12 years and college freshmen residing in dormitories by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP). Shortly thereafter in 2006, a new tetanus toxoid, diphtheria, and acellular pertussis vaccine (Tdap) was recommended, and in March 2007 the quadrivalent human papillomavirus vaccine (HPV4: types 6, 11, 16, and 18) was recommended for use in girls, starting at age 11-12 years, and young women up to 26 years of age. In 2009, a bivalent HPV vaccine (HPV2: types 16 and 18) was licensed, and in 2010, ACIP recommendations indicated that either HPV4 or HPV2 vaccine could be administered to girls and young women. In addition, the use of HPV4 vaccine in males was permitted. In 2011, ACIP recommended routine administration of HPV4 to boys and young adult males up to 21 years of age. Adolescents were the target population for these vaccines, and administration was recommended at the 11- to 12-year wellness visit. The primary role of the adolescent encounter was no longer to provide catch-up immunizations. A definitive adolescent immunization schedule had been established.

Why introduce the HPV vaccine so early?

HPV is the most common sexually transmitted infection in both men and women. Recent data suggest that approximately 79 million individuals are infected (Sex. Transm. Dis. 2013;40:187-93). Annually, about 14 million, mostly young adults are infected. Most sexually active individuals will acquire HPV. It is most common in teens and young adults, and intercourse is not required for transmission. It can be transmitted with any type of intimate sexual contact, and it has been isolated from virgins. The majority of these infections are asymptomatic and self- limited. However, persistent infection is associated with cervical and other types of anogenital cancer, and genital warts in both men and women. Complications of these infections may take years to manifest.

HPV is categorized by its epidemiologic association with cervical cancer. High-risk types cause cervical cancer, and HPV types 16 and 18 account for the majority of cervical cancers (66%) These two types are also associated with vaginal (55%), anal (79%), and oropharyngeal (62%) cancer (MMWR 2014 Jan. 31;63;69-72). It is estimated that each year there are 26,000 HPV-related cancers including 8,800 cases in men and 17,000 in women, 4,000 of whom will die of cervical cancer, according to the CDC. Low-risk types including HPV types 6 and 11 cause benign/low-grade cervical cell changes, recurrent papillomatosis, and 90% of the cases of genital warts.

Once a person is infected, HPV usually clears. If not, cervical intraepithelial neoplasia (CIN) may occur. The infection may still resolve spontaneously. If it persists, the degree of dysplasia can progress. Several years may pass before progression to invasive cancer. HPV vaccines are prophylactic like other vaccines. They cannot prevent disease progression and need to be administered before exposure to the viruses.

Compared with the introduction of other vaccines, such as Haemophilus influenzae type b and Prevnar7, some pediatric care providers may feel we may not have the benefit of realizing our efforts as immediately as in the past. However, encouraging vaccine effectiveness data in U.S. teens has been published. In one study, the investigators compared HPV prevalence data from the pre- and postvaccine era collected during the National Health and Nutrition Examination Survey. Among females aged 14-19 years, HPV prevalence (HPV-6, -11, -16, or -18 ) decreased from 11.5% in 2003-2006 to 5.1% in 2007-2010. That is a 56% reduction in vaccine type HPV prevalence. This decrease in prevalence occurred within 4 years of vaccine introduction and low vaccine uptake. (J. Infect. Dis. 2013;208:385-93). Studies conducted in Denmark, Australia, Germany, and New Zealand also have shown significant declines in HPV4 vaccine type infection prevalence.

Vaccination coverage

The CDC tracks vaccination coverage annually in the National Immunization Survey–Teen (NIS-Teen), with data obtained from the 50 states, the District of Columbia, the U.S. Virgin Islands, and six major urban areas (MMWR 2013;62:685-93). Vaccination coverage differed significantly although each vaccine is recommended to be routinely administered at the 11- to 12-year visit. Although an increase from 25% to 53% had been noted between 2007 and 2011, in 2012, coverage for receiving at least one dose of HPV among females was almost 54%, essentially unchanged since 2011. The number who had received the recommended three doses was also essentially unchanged from 2011 to 2012 (34.8% in 2011 and 33.4% in 2012). Receipt of a single dose of HPV in boys was 8.3% in 2011 and 20.8% in 2012, the first year after the vaccine was recommended. Completion of the series in boys was 6.3%, an increase from 1.3% in 2011.

 

In contrast, the 2012 coverage for Tdap increased to 85% and MCV4, to 74%. It has been suggested that the higher coverage of Tdap and MCV may be due to the 40 and 13 states, respectively, that require them for middle school entry.

The disparity in coverage between Tdap and other vaccines suggests there are numerous missed opportunities to vaccinate adolescents. Data revealed that missed opportunities for girls increased from 20.8% in 2007 to 84% in 2012. If all missed opportunities had been eliminated, HPV coverage for at least one dose could have reached 92.6%.Almost 25% of parents indicated that they had no plan to immunize their daughter. The top reasons parents stated for not immunizing their daughters included: not needed or necessary, 19.1%; not recommended by provider, 14.2%; safety concerns, 13.3%; lack of knowledge, 12.6%; and not sexually active, 10.1%. (MMWR 2013;62:591-5).

Vaccine safety also was addressed. All reported adverse events were consistent with prelicensure clinical trial data. Ninety two percent of all adverse events were nonserious and included syncope, dizziness, nausea, and fever. Reports peaked in 2008 and have declined each year thereafter.

Challenges for HPV prevention

Improving immunization coverage is critical. There are numerous strategies to increase coverage including reminder recall systems, standing orders, and educating parents, patients, health care providers, and office staff who interact with parents. Education should reemphasize why immunization is initiated at 11-12 years and that completion of the series is recommended by 13 years. School requirements have always led to an increase in vaccination coverage. Only the District of Columbia has one for HPV. In this case, eliminating missed opportunities is crucial. It is estimated that for every year coverage is delayed, an additional 4,400 women will develop cervical cancer. The reality is that the burden of HPV-related cancers will persist if coverage is not increased.

As Louis Pasteur once said, "When meditating over a disease, I never think of finding a remedy for it, but, instead a means of preventing it."

For additional resources to assist with discussions about HPV, click here.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. E-mail her at [email protected]. Scan this QR code or visit pediatricnews.com.

The U.S. immunization program has been one of the country’s most successful initiatives and best investments. Prior to 2005, vaccines were targeted for administration to infants and young children. Adolescence was a period for catch-up immunizations. All that changed in 2005 when the first meningococcal conjugate vaccine (MCV) was recommended for administration to preteens at 11-12 years and college freshmen residing in dormitories by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP). Shortly thereafter in 2006, a new tetanus toxoid, diphtheria, and acellular pertussis vaccine (Tdap) was recommended, and in March 2007 the quadrivalent human papillomavirus vaccine (HPV4: types 6, 11, 16, and 18) was recommended for use in girls, starting at age 11-12 years, and young women up to 26 years of age. In 2009, a bivalent HPV vaccine (HPV2: types 16 and 18) was licensed, and in 2010, ACIP recommendations indicated that either HPV4 or HPV2 vaccine could be administered to girls and young women. In addition, the use of HPV4 vaccine in males was permitted. In 2011, ACIP recommended routine administration of HPV4 to boys and young adult males up to 21 years of age. Adolescents were the target population for these vaccines, and administration was recommended at the 11- to 12-year wellness visit. The primary role of the adolescent encounter was no longer to provide catch-up immunizations. A definitive adolescent immunization schedule had been established.

Why introduce the HPV vaccine so early?

HPV is the most common sexually transmitted infection in both men and women. Recent data suggest that approximately 79 million individuals are infected (Sex. Transm. Dis. 2013;40:187-93). Annually, about 14 million, mostly young adults are infected. Most sexually active individuals will acquire HPV. It is most common in teens and young adults, and intercourse is not required for transmission. It can be transmitted with any type of intimate sexual contact, and it has been isolated from virgins. The majority of these infections are asymptomatic and self- limited. However, persistent infection is associated with cervical and other types of anogenital cancer, and genital warts in both men and women. Complications of these infections may take years to manifest.

HPV is categorized by its epidemiologic association with cervical cancer. High-risk types cause cervical cancer, and HPV types 16 and 18 account for the majority of cervical cancers (66%) These two types are also associated with vaginal (55%), anal (79%), and oropharyngeal (62%) cancer (MMWR 2014 Jan. 31;63;69-72). It is estimated that each year there are 26,000 HPV-related cancers including 8,800 cases in men and 17,000 in women, 4,000 of whom will die of cervical cancer, according to the CDC. Low-risk types including HPV types 6 and 11 cause benign/low-grade cervical cell changes, recurrent papillomatosis, and 90% of the cases of genital warts.

Once a person is infected, HPV usually clears. If not, cervical intraepithelial neoplasia (CIN) may occur. The infection may still resolve spontaneously. If it persists, the degree of dysplasia can progress. Several years may pass before progression to invasive cancer. HPV vaccines are prophylactic like other vaccines. They cannot prevent disease progression and need to be administered before exposure to the viruses.

Compared with the introduction of other vaccines, such as Haemophilus influenzae type b and Prevnar7, some pediatric care providers may feel we may not have the benefit of realizing our efforts as immediately as in the past. However, encouraging vaccine effectiveness data in U.S. teens has been published. In one study, the investigators compared HPV prevalence data from the pre- and postvaccine era collected during the National Health and Nutrition Examination Survey. Among females aged 14-19 years, HPV prevalence (HPV-6, -11, -16, or -18 ) decreased from 11.5% in 2003-2006 to 5.1% in 2007-2010. That is a 56% reduction in vaccine type HPV prevalence. This decrease in prevalence occurred within 4 years of vaccine introduction and low vaccine uptake. (J. Infect. Dis. 2013;208:385-93). Studies conducted in Denmark, Australia, Germany, and New Zealand also have shown significant declines in HPV4 vaccine type infection prevalence.

Vaccination coverage

The CDC tracks vaccination coverage annually in the National Immunization Survey–Teen (NIS-Teen), with data obtained from the 50 states, the District of Columbia, the U.S. Virgin Islands, and six major urban areas (MMWR 2013;62:685-93). Vaccination coverage differed significantly although each vaccine is recommended to be routinely administered at the 11- to 12-year visit. Although an increase from 25% to 53% had been noted between 2007 and 2011, in 2012, coverage for receiving at least one dose of HPV among females was almost 54%, essentially unchanged since 2011. The number who had received the recommended three doses was also essentially unchanged from 2011 to 2012 (34.8% in 2011 and 33.4% in 2012). Receipt of a single dose of HPV in boys was 8.3% in 2011 and 20.8% in 2012, the first year after the vaccine was recommended. Completion of the series in boys was 6.3%, an increase from 1.3% in 2011.

 

In contrast, the 2012 coverage for Tdap increased to 85% and MCV4, to 74%. It has been suggested that the higher coverage of Tdap and MCV may be due to the 40 and 13 states, respectively, that require them for middle school entry.

The disparity in coverage between Tdap and other vaccines suggests there are numerous missed opportunities to vaccinate adolescents. Data revealed that missed opportunities for girls increased from 20.8% in 2007 to 84% in 2012. If all missed opportunities had been eliminated, HPV coverage for at least one dose could have reached 92.6%.Almost 25% of parents indicated that they had no plan to immunize their daughter. The top reasons parents stated for not immunizing their daughters included: not needed or necessary, 19.1%; not recommended by provider, 14.2%; safety concerns, 13.3%; lack of knowledge, 12.6%; and not sexually active, 10.1%. (MMWR 2013;62:591-5).

Vaccine safety also was addressed. All reported adverse events were consistent with prelicensure clinical trial data. Ninety two percent of all adverse events were nonserious and included syncope, dizziness, nausea, and fever. Reports peaked in 2008 and have declined each year thereafter.

Challenges for HPV prevention

Improving immunization coverage is critical. There are numerous strategies to increase coverage including reminder recall systems, standing orders, and educating parents, patients, health care providers, and office staff who interact with parents. Education should reemphasize why immunization is initiated at 11-12 years and that completion of the series is recommended by 13 years. School requirements have always led to an increase in vaccination coverage. Only the District of Columbia has one for HPV. In this case, eliminating missed opportunities is crucial. It is estimated that for every year coverage is delayed, an additional 4,400 women will develop cervical cancer. The reality is that the burden of HPV-related cancers will persist if coverage is not increased.

As Louis Pasteur once said, "When meditating over a disease, I never think of finding a remedy for it, but, instead a means of preventing it."

For additional resources to assist with discussions about HPV, click here.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. E-mail her at [email protected]. Scan this QR code or visit pediatricnews.com.

The U.S. immunization program has been one of the country’s most successful initiatives and best investments. Prior to 2005, vaccines were targeted for administration to infants and young children. Adolescence was a period for catch-up immunizations. All that changed in 2005 when the first meningococcal conjugate vaccine (MCV) was recommended for administration to preteens at 11-12 years and college freshmen residing in dormitories by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP). Shortly thereafter in 2006, a new tetanus toxoid, diphtheria, and acellular pertussis vaccine (Tdap) was recommended, and in March 2007 the quadrivalent human papillomavirus vaccine (HPV4: types 6, 11, 16, and 18) was recommended for use in girls, starting at age 11-12 years, and young women up to 26 years of age. In 2009, a bivalent HPV vaccine (HPV2: types 16 and 18) was licensed, and in 2010, ACIP recommendations indicated that either HPV4 or HPV2 vaccine could be administered to girls and young women. In addition, the use of HPV4 vaccine in males was permitted. In 2011, ACIP recommended routine administration of HPV4 to boys and young adult males up to 21 years of age. Adolescents were the target population for these vaccines, and administration was recommended at the 11- to 12-year wellness visit. The primary role of the adolescent encounter was no longer to provide catch-up immunizations. A definitive adolescent immunization schedule had been established.

Why introduce the HPV vaccine so early?

HPV is the most common sexually transmitted infection in both men and women. Recent data suggest that approximately 79 million individuals are infected (Sex. Transm. Dis. 2013;40:187-93). Annually, about 14 million, mostly young adults are infected. Most sexually active individuals will acquire HPV. It is most common in teens and young adults, and intercourse is not required for transmission. It can be transmitted with any type of intimate sexual contact, and it has been isolated from virgins. The majority of these infections are asymptomatic and self- limited. However, persistent infection is associated with cervical and other types of anogenital cancer, and genital warts in both men and women. Complications of these infections may take years to manifest.

HPV is categorized by its epidemiologic association with cervical cancer. High-risk types cause cervical cancer, and HPV types 16 and 18 account for the majority of cervical cancers (66%) These two types are also associated with vaginal (55%), anal (79%), and oropharyngeal (62%) cancer (MMWR 2014 Jan. 31;63;69-72). It is estimated that each year there are 26,000 HPV-related cancers including 8,800 cases in men and 17,000 in women, 4,000 of whom will die of cervical cancer, according to the CDC. Low-risk types including HPV types 6 and 11 cause benign/low-grade cervical cell changes, recurrent papillomatosis, and 90% of the cases of genital warts.

Once a person is infected, HPV usually clears. If not, cervical intraepithelial neoplasia (CIN) may occur. The infection may still resolve spontaneously. If it persists, the degree of dysplasia can progress. Several years may pass before progression to invasive cancer. HPV vaccines are prophylactic like other vaccines. They cannot prevent disease progression and need to be administered before exposure to the viruses.

Compared with the introduction of other vaccines, such as Haemophilus influenzae type b and Prevnar7, some pediatric care providers may feel we may not have the benefit of realizing our efforts as immediately as in the past. However, encouraging vaccine effectiveness data in U.S. teens has been published. In one study, the investigators compared HPV prevalence data from the pre- and postvaccine era collected during the National Health and Nutrition Examination Survey. Among females aged 14-19 years, HPV prevalence (HPV-6, -11, -16, or -18 ) decreased from 11.5% in 2003-2006 to 5.1% in 2007-2010. That is a 56% reduction in vaccine type HPV prevalence. This decrease in prevalence occurred within 4 years of vaccine introduction and low vaccine uptake. (J. Infect. Dis. 2013;208:385-93). Studies conducted in Denmark, Australia, Germany, and New Zealand also have shown significant declines in HPV4 vaccine type infection prevalence.

Vaccination coverage

The CDC tracks vaccination coverage annually in the National Immunization Survey–Teen (NIS-Teen), with data obtained from the 50 states, the District of Columbia, the U.S. Virgin Islands, and six major urban areas (MMWR 2013;62:685-93). Vaccination coverage differed significantly although each vaccine is recommended to be routinely administered at the 11- to 12-year visit. Although an increase from 25% to 53% had been noted between 2007 and 2011, in 2012, coverage for receiving at least one dose of HPV among females was almost 54%, essentially unchanged since 2011. The number who had received the recommended three doses was also essentially unchanged from 2011 to 2012 (34.8% in 2011 and 33.4% in 2012). Receipt of a single dose of HPV in boys was 8.3% in 2011 and 20.8% in 2012, the first year after the vaccine was recommended. Completion of the series in boys was 6.3%, an increase from 1.3% in 2011.

 

In contrast, the 2012 coverage for Tdap increased to 85% and MCV4, to 74%. It has been suggested that the higher coverage of Tdap and MCV may be due to the 40 and 13 states, respectively, that require them for middle school entry.

The disparity in coverage between Tdap and other vaccines suggests there are numerous missed opportunities to vaccinate adolescents. Data revealed that missed opportunities for girls increased from 20.8% in 2007 to 84% in 2012. If all missed opportunities had been eliminated, HPV coverage for at least one dose could have reached 92.6%.Almost 25% of parents indicated that they had no plan to immunize their daughter. The top reasons parents stated for not immunizing their daughters included: not needed or necessary, 19.1%; not recommended by provider, 14.2%; safety concerns, 13.3%; lack of knowledge, 12.6%; and not sexually active, 10.1%. (MMWR 2013;62:591-5).

Vaccine safety also was addressed. All reported adverse events were consistent with prelicensure clinical trial data. Ninety two percent of all adverse events were nonserious and included syncope, dizziness, nausea, and fever. Reports peaked in 2008 and have declined each year thereafter.

Challenges for HPV prevention

Improving immunization coverage is critical. There are numerous strategies to increase coverage including reminder recall systems, standing orders, and educating parents, patients, health care providers, and office staff who interact with parents. Education should reemphasize why immunization is initiated at 11-12 years and that completion of the series is recommended by 13 years. School requirements have always led to an increase in vaccination coverage. Only the District of Columbia has one for HPV. In this case, eliminating missed opportunities is crucial. It is estimated that for every year coverage is delayed, an additional 4,400 women will develop cervical cancer. The reality is that the burden of HPV-related cancers will persist if coverage is not increased.

As Louis Pasteur once said, "When meditating over a disease, I never think of finding a remedy for it, but, instead a means of preventing it."

For additional resources to assist with discussions about HPV, click here.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. E-mail her at [email protected]. Scan this QR code or visit pediatricnews.com.

Are you prepared to manage the infectious disease challenges you’ll be facing in 2014? Here are my Top 5 predictions for what lies ahead in infectious diseases for the next year with pearls to help you in your practice. The first addresses a series of concerns around influenza. Others target diagnoses you might not have encountered or considered in the past. The last will hopefully improve HPV vaccination rates in your practice.

1. Expect an especially busy influenza season and the possibility that you may encounter patients with life-threatening influenza. We’ve already detected influenza in over 1,000 children at my institution, almost all 2009 pandemic H1N1 influenza A viruses, which is consistent with the national data from the Centers for Disease Control and Prevention. We are really just a month into influenza season, and we are seeing a significant number of children admitted to our pediatric intensive care unit with life-threatening disease presentations, and we’ve also seen unusual influenza complications. Talk to your ID colleagues about the potential for intravenous zanamivir in critically ill children who do not respond to oseltamivir. While pulmonary complications of influenza are most common, unusual presentations you may encounter include influenza encephalopathy (altered mental status, seizures, and mutism) and bacterial superinfection (when fever recurs or recrudesces after initial improvement, often 3-5 days into the course, think Staphylococcus aureus or Group A streptococcal disease). The CDC is alerting practitioners to the potential for increased morbidity and mortality in young/middle aged adults so the parents of your patients are at increased risk this year.

• False-negative testing can happen if the sensitivity of the rapid test is low, but a false-negative test can occur if the specimen is collected late in the clinical course. (This is especially true in the adult population in which testing may be negative at just 4-5 days into the course of disease.)

• Recognize that all hospitalized children should be treated with oseltamivir, as well as children who are immunocompromised; have chronic cardiopulmonary conditions, including hemodynamically significant heart disease and asthma; renal disease; metabolic disease, including diabetes; pregnant teens; morbidly obese patients; patients with neuromuscular/neurodevelopmental conditions (especially those with difficulty controlling airway secretions); and children under 2 years of age.

• I predict you may be hearing about oseltamivir shortages, but for now this relates to the sporadic difficulty in finding the oseltamivir suspension, in part, because of the lack of early season availability of this product at retail pharmacies, many of which are just getting in their stock. Prescribe the suspension for children aged younger than 1 year and be explicit about the mL dosage that should be dispensed. For children over 1 year of age, capsules can be opened and placed in pudding for those who cannot swallow capsules. Lexicomp Online offers guidelines for easy use of 30-mg, 45-mg and 75-mg capsules for different weight categories. If the suspension is necessary for an infant and is not available, the drug can be compounded by your pharmacy using capsules. You may find some pharmacies are reluctant to compound, so be prepared to contact your local children’s hospital for help. And keep offering vaccine throughout the season to healthy patients!

2. Most practitioners are aware of the importance of methicillin-resistant S. aureus (MRSA) as a pathogen that causes bacteremia and musculoskeletal and pulmonary disease in otherwise healthy children. I suspect there is less awareness that, in many locales, methicillin-sensitive S. aureus (MSSA) is being seen just as often, if not slightly more often than MRSA, as a bloodstream pathogen. The inclusion of vancomycin (which covers MRSA) with cefepime should be considered for empiric coverage in the otherwise healthy child with suspected sepsis. Cefepime is a fourth-generation cephalosporin with good gram-negative and gram-positive coverage and also has bactericidal activity against MSSA strains. Clindamycin should be considered as an adjunct to vancomycin and cefepime in those with toxin-mediated disease/toxic shock syndrome. Of course, modification of the empiric regimen should follow identification of the specific pathogen and the site(s) of infection.

3. E. coli remains the most common cause of urinary tract infections in children, but infections caused by multiple drug resistant (MDR) Escherichia coli strains are increasingly being seen. Consider infection caused by extended spectrum beta-lactamase–producing organisms in children with underlying renal anomalies, especially if they have been previously exposed to third-generation cephalosporins. Most strains are also resistant to fluoroquinolones, trimethoprim-sulfamethoxazole, and aminoglycosides as well as to non–carbapenem beta-lactams. Speaking of antibiotic resistance, look for many hospital microbiology laboratories to begin using advanced molecular detection methodology to more quickly identify bacterial and fungal isolates; such methods could reduce the time of identification from over 24 hours with conventional techniques to less than one hour. The use of newer systems to identify microbes and confirm susceptibility testing has the potential to transform care and improve outcomes.

 

4. Consider the diagnosis of human parechovirus (HPeV) infection in young febrile infants with sepsis/meningitis presentation but negative bacterial cultures. Detection of HPeV by polymerase chain reaction testing in serum or cerebrospinal fluid is diagnostic. Exclusion of herpes simplex virus and enterovirus disease is key, as similar clinical presentations may be seen. HPeV infections are more commonly noted in late spring and early summer in contrast to enteroviral infections, which tend to occur from July to September.

5. The strength of your vaccine recommendation continues to be the most important factor affecting the parental decision to vaccinate a child. Nowhere is this more obvious than with human papillomavirus vaccine (HPV), where practitioners often simply offer the vaccine rather than recommend it. In terms of teenage vaccines, when practitioners recommend Tdap (tetanus, diphtheria, and pertussis vaccine) and meningococcal conjugate vaccine as standard for their patients ("Today your child will receive whooping cough vaccine and the meningitis vaccine."), vaccine uptake is very high. But when it comes to the HPV vaccine, some practitioners feel they first must establish whether the parents are aware of HPV vaccine; then discuss their questions regarding the safety of the vaccine; and finally, explain that the vaccine prevents cancer. Some practitioners offer the option of "thinking about" the vaccine for the next visit, but in such cases, the patient generally leaves without receiving the vaccine. Add HPV vaccine into your standard teen vaccine recommendation and make it a goal to get the first vaccine initiated in all eligible patients. The three-dose HPV vaccine schedule is still recommended, but I predict that simplification of the schedule may occur as early as 2014 in the United States. We’ll keep you posted.

Dr. Jackson is director of the division of infectious disease and associate director of the infectious disease fellowship program at the University of Missouri, Kansas City.

Are you prepared to manage the infectious disease challenges you’ll be facing in 2014? Here are my Top 5 predictions for what lies ahead in infectious diseases for the next year with pearls to help you in your practice. The first addresses a series of concerns around influenza. Others target diagnoses you might not have encountered or considered in the past. The last will hopefully improve HPV vaccination rates in your practice.

1. Expect an especially busy influenza season and the possibility that you may encounter patients with life-threatening influenza. We’ve already detected influenza in over 1,000 children at my institution, almost all 2009 pandemic H1N1 influenza A viruses, which is consistent with the national data from the Centers for Disease Control and Prevention. We are really just a month into influenza season, and we are seeing a significant number of children admitted to our pediatric intensive care unit with life-threatening disease presentations, and we’ve also seen unusual influenza complications. Talk to your ID colleagues about the potential for intravenous zanamivir in critically ill children who do not respond to oseltamivir. While pulmonary complications of influenza are most common, unusual presentations you may encounter include influenza encephalopathy (altered mental status, seizures, and mutism) and bacterial superinfection (when fever recurs or recrudesces after initial improvement, often 3-5 days into the course, think Staphylococcus aureus or Group A streptococcal disease). The CDC is alerting practitioners to the potential for increased morbidity and mortality in young/middle aged adults so the parents of your patients are at increased risk this year.

• False-negative testing can happen if the sensitivity of the rapid test is low, but a false-negative test can occur if the specimen is collected late in the clinical course. (This is especially true in the adult population in which testing may be negative at just 4-5 days into the course of disease.)

• Recognize that all hospitalized children should be treated with oseltamivir, as well as children who are immunocompromised; have chronic cardiopulmonary conditions, including hemodynamically significant heart disease and asthma; renal disease; metabolic disease, including diabetes; pregnant teens; morbidly obese patients; patients with neuromuscular/neurodevelopmental conditions (especially those with difficulty controlling airway secretions); and children under 2 years of age.

• I predict you may be hearing about oseltamivir shortages, but for now this relates to the sporadic difficulty in finding the oseltamivir suspension, in part, because of the lack of early season availability of this product at retail pharmacies, many of which are just getting in their stock. Prescribe the suspension for children aged younger than 1 year and be explicit about the mL dosage that should be dispensed. For children over 1 year of age, capsules can be opened and placed in pudding for those who cannot swallow capsules. Lexicomp Online offers guidelines for easy use of 30-mg, 45-mg and 75-mg capsules for different weight categories. If the suspension is necessary for an infant and is not available, the drug can be compounded by your pharmacy using capsules. You may find some pharmacies are reluctant to compound, so be prepared to contact your local children’s hospital for help. And keep offering vaccine throughout the season to healthy patients!

2. Most practitioners are aware of the importance of methicillin-resistant S. aureus (MRSA) as a pathogen that causes bacteremia and musculoskeletal and pulmonary disease in otherwise healthy children. I suspect there is less awareness that, in many locales, methicillin-sensitive S. aureus (MSSA) is being seen just as often, if not slightly more often than MRSA, as a bloodstream pathogen. The inclusion of vancomycin (which covers MRSA) with cefepime should be considered for empiric coverage in the otherwise healthy child with suspected sepsis. Cefepime is a fourth-generation cephalosporin with good gram-negative and gram-positive coverage and also has bactericidal activity against MSSA strains. Clindamycin should be considered as an adjunct to vancomycin and cefepime in those with toxin-mediated disease/toxic shock syndrome. Of course, modification of the empiric regimen should follow identification of the specific pathogen and the site(s) of infection.

3. E. coli remains the most common cause of urinary tract infections in children, but infections caused by multiple drug resistant (MDR) Escherichia coli strains are increasingly being seen. Consider infection caused by extended spectrum beta-lactamase–producing organisms in children with underlying renal anomalies, especially if they have been previously exposed to third-generation cephalosporins. Most strains are also resistant to fluoroquinolones, trimethoprim-sulfamethoxazole, and aminoglycosides as well as to non–carbapenem beta-lactams. Speaking of antibiotic resistance, look for many hospital microbiology laboratories to begin using advanced molecular detection methodology to more quickly identify bacterial and fungal isolates; such methods could reduce the time of identification from over 24 hours with conventional techniques to less than one hour. The use of newer systems to identify microbes and confirm susceptibility testing has the potential to transform care and improve outcomes.

 

4. Consider the diagnosis of human parechovirus (HPeV) infection in young febrile infants with sepsis/meningitis presentation but negative bacterial cultures. Detection of HPeV by polymerase chain reaction testing in serum or cerebrospinal fluid is diagnostic. Exclusion of herpes simplex virus and enterovirus disease is key, as similar clinical presentations may be seen. HPeV infections are more commonly noted in late spring and early summer in contrast to enteroviral infections, which tend to occur from July to September.

5. The strength of your vaccine recommendation continues to be the most important factor affecting the parental decision to vaccinate a child. Nowhere is this more obvious than with human papillomavirus vaccine (HPV), where practitioners often simply offer the vaccine rather than recommend it. In terms of teenage vaccines, when practitioners recommend Tdap (tetanus, diphtheria, and pertussis vaccine) and meningococcal conjugate vaccine as standard for their patients ("Today your child will receive whooping cough vaccine and the meningitis vaccine."), vaccine uptake is very high. But when it comes to the HPV vaccine, some practitioners feel they first must establish whether the parents are aware of HPV vaccine; then discuss their questions regarding the safety of the vaccine; and finally, explain that the vaccine prevents cancer. Some practitioners offer the option of "thinking about" the vaccine for the next visit, but in such cases, the patient generally leaves without receiving the vaccine. Add HPV vaccine into your standard teen vaccine recommendation and make it a goal to get the first vaccine initiated in all eligible patients. The three-dose HPV vaccine schedule is still recommended, but I predict that simplification of the schedule may occur as early as 2014 in the United States. We’ll keep you posted.

Dr. Jackson is director of the division of infectious disease and associate director of the infectious disease fellowship program at the University of Missouri, Kansas City.

Are you prepared to manage the infectious disease challenges you’ll be facing in 2014? Here are my Top 5 predictions for what lies ahead in infectious diseases for the next year with pearls to help you in your practice. The first addresses a series of concerns around influenza. Others target diagnoses you might not have encountered or considered in the past. The last will hopefully improve HPV vaccination rates in your practice.

1. Expect an especially busy influenza season and the possibility that you may encounter patients with life-threatening influenza. We’ve already detected influenza in over 1,000 children at my institution, almost all 2009 pandemic H1N1 influenza A viruses, which is consistent with the national data from the Centers for Disease Control and Prevention. We are really just a month into influenza season, and we are seeing a significant number of children admitted to our pediatric intensive care unit with life-threatening disease presentations, and we’ve also seen unusual influenza complications. Talk to your ID colleagues about the potential for intravenous zanamivir in critically ill children who do not respond to oseltamivir. While pulmonary complications of influenza are most common, unusual presentations you may encounter include influenza encephalopathy (altered mental status, seizures, and mutism) and bacterial superinfection (when fever recurs or recrudesces after initial improvement, often 3-5 days into the course, think Staphylococcus aureus or Group A streptococcal disease). The CDC is alerting practitioners to the potential for increased morbidity and mortality in young/middle aged adults so the parents of your patients are at increased risk this year.

• False-negative testing can happen if the sensitivity of the rapid test is low, but a false-negative test can occur if the specimen is collected late in the clinical course. (This is especially true in the adult population in which testing may be negative at just 4-5 days into the course of disease.)

• Recognize that all hospitalized children should be treated with oseltamivir, as well as children who are immunocompromised; have chronic cardiopulmonary conditions, including hemodynamically significant heart disease and asthma; renal disease; metabolic disease, including diabetes; pregnant teens; morbidly obese patients; patients with neuromuscular/neurodevelopmental conditions (especially those with difficulty controlling airway secretions); and children under 2 years of age.

• I predict you may be hearing about oseltamivir shortages, but for now this relates to the sporadic difficulty in finding the oseltamivir suspension, in part, because of the lack of early season availability of this product at retail pharmacies, many of which are just getting in their stock. Prescribe the suspension for children aged younger than 1 year and be explicit about the mL dosage that should be dispensed. For children over 1 year of age, capsules can be opened and placed in pudding for those who cannot swallow capsules. Lexicomp Online offers guidelines for easy use of 30-mg, 45-mg and 75-mg capsules for different weight categories. If the suspension is necessary for an infant and is not available, the drug can be compounded by your pharmacy using capsules. You may find some pharmacies are reluctant to compound, so be prepared to contact your local children’s hospital for help. And keep offering vaccine throughout the season to healthy patients!

2. Most practitioners are aware of the importance of methicillin-resistant S. aureus (MRSA) as a pathogen that causes bacteremia and musculoskeletal and pulmonary disease in otherwise healthy children. I suspect there is less awareness that, in many locales, methicillin-sensitive S. aureus (MSSA) is being seen just as often, if not slightly more often than MRSA, as a bloodstream pathogen. The inclusion of vancomycin (which covers MRSA) with cefepime should be considered for empiric coverage in the otherwise healthy child with suspected sepsis. Cefepime is a fourth-generation cephalosporin with good gram-negative and gram-positive coverage and also has bactericidal activity against MSSA strains. Clindamycin should be considered as an adjunct to vancomycin and cefepime in those with toxin-mediated disease/toxic shock syndrome. Of course, modification of the empiric regimen should follow identification of the specific pathogen and the site(s) of infection.

3. E. coli remains the most common cause of urinary tract infections in children, but infections caused by multiple drug resistant (MDR) Escherichia coli strains are increasingly being seen. Consider infection caused by extended spectrum beta-lactamase–producing organisms in children with underlying renal anomalies, especially if they have been previously exposed to third-generation cephalosporins. Most strains are also resistant to fluoroquinolones, trimethoprim-sulfamethoxazole, and aminoglycosides as well as to non–carbapenem beta-lactams. Speaking of antibiotic resistance, look for many hospital microbiology laboratories to begin using advanced molecular detection methodology to more quickly identify bacterial and fungal isolates; such methods could reduce the time of identification from over 24 hours with conventional techniques to less than one hour. The use of newer systems to identify microbes and confirm susceptibility testing has the potential to transform care and improve outcomes.

 

4. Consider the diagnosis of human parechovirus (HPeV) infection in young febrile infants with sepsis/meningitis presentation but negative bacterial cultures. Detection of HPeV by polymerase chain reaction testing in serum or cerebrospinal fluid is diagnostic. Exclusion of herpes simplex virus and enterovirus disease is key, as similar clinical presentations may be seen. HPeV infections are more commonly noted in late spring and early summer in contrast to enteroviral infections, which tend to occur from July to September.

5. The strength of your vaccine recommendation continues to be the most important factor affecting the parental decision to vaccinate a child. Nowhere is this more obvious than with human papillomavirus vaccine (HPV), where practitioners often simply offer the vaccine rather than recommend it. In terms of teenage vaccines, when practitioners recommend Tdap (tetanus, diphtheria, and pertussis vaccine) and meningococcal conjugate vaccine as standard for their patients ("Today your child will receive whooping cough vaccine and the meningitis vaccine."), vaccine uptake is very high. But when it comes to the HPV vaccine, some practitioners feel they first must establish whether the parents are aware of HPV vaccine; then discuss their questions regarding the safety of the vaccine; and finally, explain that the vaccine prevents cancer. Some practitioners offer the option of "thinking about" the vaccine for the next visit, but in such cases, the patient generally leaves without receiving the vaccine. Add HPV vaccine into your standard teen vaccine recommendation and make it a goal to get the first vaccine initiated in all eligible patients. The three-dose HPV vaccine schedule is still recommended, but I predict that simplification of the schedule may occur as early as 2014 in the United States. We’ll keep you posted.

Dr. Jackson is director of the division of infectious disease and associate director of the infectious disease fellowship program at the University of Missouri, Kansas City.

Spectral gradient acoustic reflectometer (SGAR) is a technology to assist in the detection of middle ear fluid occurring in the context of diagnosing acute otitis media (AOM) and otitis media with effusion (OME). The technology involves sending a harmless, inaudible sonar-like sound wave from the emitter that goes through the tympanic membrane, hits the posterior wall of the middle ear space, and bounces back to the sound detector in the device. If there is only air in the middle ear space, the sound wave bounces back quickly, and you get a high reading. If the sound wave bounces back more slowly, there is middle ear effusion. The thicker the effusion, the more likely it is pus and an AOM or a chronic OME (depending on the clinical situation), causing the sound wave to bounce back more slowly and giving a low reading.

The specificity of a high reading is remarkable at around 95%, so a high reading is a big reassurance that middle ear effusion is absent. A lower reading suggests effusion and the lower it is, the greater the sensitivity. When I get an unexpected higher or lower reading, I go back and reexamine the patient.

I asked our nurses to compare the handheld tympanometer to the SGAR. They actually perform the testing, and I interpret it. The nurses said:

• The SGAR is easier to use because of how quickly a readout is obtained.

• If a child is crying or moving, they can still get a readout.

• You don’t have to change the tip of the SGAR for the size of the external ear canal.

• The SGAR is easier to read than the tympanometer.

• The SGAR is easier to interpret for the parents.

• You don’t have to get a seal with the ear canal with SGAR, as you do with a tympanometer.

• The SGAR uses a disposable tip.

I asked our office manager to look up our use of the SGAR and tympanometer during our everyday practice. We found that SGAR or tympanometry was used in 12% of patient encounters in which the diagnosis of AOM or OME was part of the chief complaint. The ratio of use was 3:1, favoring SGAR. The most frequent use was in 30% of patient encounters tied to the diagnosis of "otalgia" (388.70) because with that diagnosis, we are stating to parents and patients that there is no middle ear pathology seen on exam, and it is confirmed by a test using sonar waves with the SGAR device. Our nurse practitioners and physician assistants particularly find the use of the SGAR beneficial in helping to reassure the parents and patients that they have not missed an AOM or OME.

The billing code is the same for SGAR and tympanometry (92567), so the fee payment is the same for both tests. Our second most common use is in association with possible AOM (382.9) at 12% of visits. Third is OME (381.02) used in a follow-up visit to determine the presence and thickness of persisting effusion.

About one-quarter of children seen in our practice with a chief complaint of "earache" receive the diagnosis of otalgia, often confirmed by SGAR, and do not receive an antibiotic. Thus, they are offsetting the charge for the procedure by saving on the costs of antibiotics and the accumulation of excessive diagnoses of AOM and OME leading to ear tube surgeries and tonsillectomy/adenoidectomy. The diagnosis of AOM and OME requires a middle ear effusion to be accurate, and only SGAR measures detection of middle ear effusion. SGAR is a must own device for clinicians who exam ears. SGAR can help in conjunction with otoscopy for a difficult diagnosis of AOM. If I am having troubleremoving wax, or if the external ear canal is particularly curved, or if I’m on the fence or the parent seems to need further evidence of my diagnosis, I turn to the SGAR. If I can get a reading, then it can really help, and my nurses are successful in getting a reading about 90% of the time. The main issue is ear canal wax, because occlusion by wax of more than 50% of the external ear canal opening causes invalid readings.

We should prescribe antibiotics for AOM in my opinion, but not for otalgia and not if the diagnosis is uncertain. The SGAR device when properly used can help to reduce unnecessary use of antibiotics and their complications. In prior "ID Consult" columns, I have discussed improving the diagnostic accuracy of AOM and OME. Performing a good otoscopic exam with the best tools available and combining that exam with SGAR or tympanometry, in selected cases, is the best practice in my opinion, and what I do in my own practice.

 

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute, Rochester General Hospital, N.Y. He is also a pediatrician at Legacy Pediatrics in Rochester. E-mail him at [email protected]. Innovia Medical, the company that is bringing the SGAR EarCheck Pro back to market in 2014 after improvement and the addition of a USB port to allow the import of the data readout into the electronic medical record, asked Dr. Pichichero to assess the SGAR device.

Spectral gradient acoustic reflectometer (SGAR) is a technology to assist in the detection of middle ear fluid occurring in the context of diagnosing acute otitis media (AOM) and otitis media with effusion (OME). The technology involves sending a harmless, inaudible sonar-like sound wave from the emitter that goes through the tympanic membrane, hits the posterior wall of the middle ear space, and bounces back to the sound detector in the device. If there is only air in the middle ear space, the sound wave bounces back quickly, and you get a high reading. If the sound wave bounces back more slowly, there is middle ear effusion. The thicker the effusion, the more likely it is pus and an AOM or a chronic OME (depending on the clinical situation), causing the sound wave to bounce back more slowly and giving a low reading.

The specificity of a high reading is remarkable at around 95%, so a high reading is a big reassurance that middle ear effusion is absent. A lower reading suggests effusion and the lower it is, the greater the sensitivity. When I get an unexpected higher or lower reading, I go back and reexamine the patient.

I asked our nurses to compare the handheld tympanometer to the SGAR. They actually perform the testing, and I interpret it. The nurses said:

• The SGAR is easier to use because of how quickly a readout is obtained.

• If a child is crying or moving, they can still get a readout.

• You don’t have to change the tip of the SGAR for the size of the external ear canal.

• The SGAR is easier to read than the tympanometer.

• The SGAR is easier to interpret for the parents.

• You don’t have to get a seal with the ear canal with SGAR, as you do with a tympanometer.

• The SGAR uses a disposable tip.

I asked our office manager to look up our use of the SGAR and tympanometer during our everyday practice. We found that SGAR or tympanometry was used in 12% of patient encounters in which the diagnosis of AOM or OME was part of the chief complaint. The ratio of use was 3:1, favoring SGAR. The most frequent use was in 30% of patient encounters tied to the diagnosis of "otalgia" (388.70) because with that diagnosis, we are stating to parents and patients that there is no middle ear pathology seen on exam, and it is confirmed by a test using sonar waves with the SGAR device. Our nurse practitioners and physician assistants particularly find the use of the SGAR beneficial in helping to reassure the parents and patients that they have not missed an AOM or OME.

The billing code is the same for SGAR and tympanometry (92567), so the fee payment is the same for both tests. Our second most common use is in association with possible AOM (382.9) at 12% of visits. Third is OME (381.02) used in a follow-up visit to determine the presence and thickness of persisting effusion.

About one-quarter of children seen in our practice with a chief complaint of "earache" receive the diagnosis of otalgia, often confirmed by SGAR, and do not receive an antibiotic. Thus, they are offsetting the charge for the procedure by saving on the costs of antibiotics and the accumulation of excessive diagnoses of AOM and OME leading to ear tube surgeries and tonsillectomy/adenoidectomy. The diagnosis of AOM and OME requires a middle ear effusion to be accurate, and only SGAR measures detection of middle ear effusion. SGAR is a must own device for clinicians who exam ears. SGAR can help in conjunction with otoscopy for a difficult diagnosis of AOM. If I am having troubleremoving wax, or if the external ear canal is particularly curved, or if I’m on the fence or the parent seems to need further evidence of my diagnosis, I turn to the SGAR. If I can get a reading, then it can really help, and my nurses are successful in getting a reading about 90% of the time. The main issue is ear canal wax, because occlusion by wax of more than 50% of the external ear canal opening causes invalid readings.

We should prescribe antibiotics for AOM in my opinion, but not for otalgia and not if the diagnosis is uncertain. The SGAR device when properly used can help to reduce unnecessary use of antibiotics and their complications. In prior "ID Consult" columns, I have discussed improving the diagnostic accuracy of AOM and OME. Performing a good otoscopic exam with the best tools available and combining that exam with SGAR or tympanometry, in selected cases, is the best practice in my opinion, and what I do in my own practice.

 

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute, Rochester General Hospital, N.Y. He is also a pediatrician at Legacy Pediatrics in Rochester. E-mail him at [email protected]. Innovia Medical, the company that is bringing the SGAR EarCheck Pro back to market in 2014 after improvement and the addition of a USB port to allow the import of the data readout into the electronic medical record, asked Dr. Pichichero to assess the SGAR device.

Spectral gradient acoustic reflectometer (SGAR) is a technology to assist in the detection of middle ear fluid occurring in the context of diagnosing acute otitis media (AOM) and otitis media with effusion (OME). The technology involves sending a harmless, inaudible sonar-like sound wave from the emitter that goes through the tympanic membrane, hits the posterior wall of the middle ear space, and bounces back to the sound detector in the device. If there is only air in the middle ear space, the sound wave bounces back quickly, and you get a high reading. If the sound wave bounces back more slowly, there is middle ear effusion. The thicker the effusion, the more likely it is pus and an AOM or a chronic OME (depending on the clinical situation), causing the sound wave to bounce back more slowly and giving a low reading.

The specificity of a high reading is remarkable at around 95%, so a high reading is a big reassurance that middle ear effusion is absent. A lower reading suggests effusion and the lower it is, the greater the sensitivity. When I get an unexpected higher or lower reading, I go back and reexamine the patient.

I asked our nurses to compare the handheld tympanometer to the SGAR. They actually perform the testing, and I interpret it. The nurses said:

• The SGAR is easier to use because of how quickly a readout is obtained.

• If a child is crying or moving, they can still get a readout.

• You don’t have to change the tip of the SGAR for the size of the external ear canal.

• The SGAR is easier to read than the tympanometer.

• The SGAR is easier to interpret for the parents.

• You don’t have to get a seal with the ear canal with SGAR, as you do with a tympanometer.

• The SGAR uses a disposable tip.

I asked our office manager to look up our use of the SGAR and tympanometer during our everyday practice. We found that SGAR or tympanometry was used in 12% of patient encounters in which the diagnosis of AOM or OME was part of the chief complaint. The ratio of use was 3:1, favoring SGAR. The most frequent use was in 30% of patient encounters tied to the diagnosis of "otalgia" (388.70) because with that diagnosis, we are stating to parents and patients that there is no middle ear pathology seen on exam, and it is confirmed by a test using sonar waves with the SGAR device. Our nurse practitioners and physician assistants particularly find the use of the SGAR beneficial in helping to reassure the parents and patients that they have not missed an AOM or OME.

The billing code is the same for SGAR and tympanometry (92567), so the fee payment is the same for both tests. Our second most common use is in association with possible AOM (382.9) at 12% of visits. Third is OME (381.02) used in a follow-up visit to determine the presence and thickness of persisting effusion.

About one-quarter of children seen in our practice with a chief complaint of "earache" receive the diagnosis of otalgia, often confirmed by SGAR, and do not receive an antibiotic. Thus, they are offsetting the charge for the procedure by saving on the costs of antibiotics and the accumulation of excessive diagnoses of AOM and OME leading to ear tube surgeries and tonsillectomy/adenoidectomy. The diagnosis of AOM and OME requires a middle ear effusion to be accurate, and only SGAR measures detection of middle ear effusion. SGAR is a must own device for clinicians who exam ears. SGAR can help in conjunction with otoscopy for a difficult diagnosis of AOM. If I am having troubleremoving wax, or if the external ear canal is particularly curved, or if I’m on the fence or the parent seems to need further evidence of my diagnosis, I turn to the SGAR. If I can get a reading, then it can really help, and my nurses are successful in getting a reading about 90% of the time. The main issue is ear canal wax, because occlusion by wax of more than 50% of the external ear canal opening causes invalid readings.

We should prescribe antibiotics for AOM in my opinion, but not for otalgia and not if the diagnosis is uncertain. The SGAR device when properly used can help to reduce unnecessary use of antibiotics and their complications. In prior "ID Consult" columns, I have discussed improving the diagnostic accuracy of AOM and OME. Performing a good otoscopic exam with the best tools available and combining that exam with SGAR or tympanometry, in selected cases, is the best practice in my opinion, and what I do in my own practice.

 

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute, Rochester General Hospital, N.Y. He is also a pediatrician at Legacy Pediatrics in Rochester. E-mail him at [email protected]. Innovia Medical, the company that is bringing the SGAR EarCheck Pro back to market in 2014 after improvement and the addition of a USB port to allow the import of the data readout into the electronic medical record, asked Dr. Pichichero to assess the SGAR device.