Safety and Immunogenicity of Full-Dose Trivalent Inactivated Influenza Vaccine (TIV) Compared With Half-Dose TIV Administered to Children 6 Through 35 Months of Age.

BACKGROUND: Children 6 through 35 months of age are recommended to receive half the dose of influenza vaccine compared with older children and adults. METHODS: This was a 6-site, randomized 2:1, double-blind study comparing full-dose (0.5 mL) trivalent inactivated influenza vaccine (TIV) with half-dose (0.25 mL) TIV in children 6 through 35 months of age. Children previously immunized with influenza vaccine (primed cohort) received 1 dose, and those with no previous influenza immunizations (naive cohort) received 2 doses of TIV. Local and systemic adverse events were recorded. Sera were collected before immunization and 1 month after last dose of TIV. Hemagglutination inhibition antibody testing was performed. RESULTS: Of the 243 subjects enrolled (32 primed, 211 naive), data for 232 were available for complete analysis. No significant differences in local or systemic reactions were observed. Few significant differences in immunogenicity to the 3 vaccine antigens were noted. The immune response to H1N1 was significantly higher in the full-dose group among primed subjects. In the naive cohort, the geometric mean titer for all 3 antigens after 2 doses of TIV were significantly higher in the 12 through 35 months compared with the 6 through 11 months age group. CONCLUSIONS: Our study confirms the safety of full-dose TIV given to children 6 through 35 months of age. An increase in antibody responses after full- versus half-dose TIV was not observed, except for H1N1 in the primed group. Larger studies are needed to clarify the potential for improved immunogenicity with higher vaccine doses. Recommending the same dose could simplify the production, storage, and administration of influenza vaccines.

Infectious complications of intrathecal baclofen pump devices in a pediatric population.

BACKGROUND: Intrathecal baclofen (ITB) is an effective therapy for spasticity and dystonia in pediatric populations; however, there are associated infectious complications. METHODS: Patients who had an initial ITB device implanted at our center were followed to determine the proportion of patients with infectious and noninfectious complications, identify risk factors for infection and describe the clinical presentations, treatment and outcomes of infectious complications. RESULTS: Over the 15-year study period, 139 patients had an initial ITB device placed. The mean age at placement was 13.6 years (range: 6 months to 41 years). In the first year of follow-up, 83% had no complications or secondary procedures, 17% had at least 1 secondary procedure and 5% had an infectious complication. The median time until infection was 14 days (mean 33 ± 42 days). Patients with secondary spasticity or dystonia were more likely to have infections than patients with cerebral palsy (86% versus 14%; P < 0.0001). In the 94 patients with a first secondary procedure, 29% had at least 1 other procedure and 8% had an infection in the 1 year follow-up. Overall, 24 patients had 27 infections; 22% superficial, 33% deep and 45% organ space. Staphylococcus aureus was isolated in 50% of those with cultures obtained. Explantation was required in 59% of patients with an infection and differed by infection type: superficial (17%), deep (44%) and organ space (92%) (P = 0.004). CONCLUSIONS: Infectious complications were relatively uncommon; however, when present, frequently led to the explantation of the ITB pump device.

Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America.

The guideline is intended for use by healthcare providers who care for adult and pediatric patients with group A streptococcal pharyngitis. The guideline updates the 2002 Infectious Diseases Society of America guideline and discusses diagnosis and management, and recommendations are provided regarding antibiotic choices and dosing. Penicillin or amoxicillin remain the treatments of choice, and recommendations are made for the penicillin-allergic patient, which now include clindamycin.

Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America.

The guideline is intended for use by healthcare providers who care for adult and pediatric patients with group A streptococcal pharyngitis. The guideline updates the 2002 Infectious Diseases Society of America guideline and discusses diagnosis and management, and recommendations are provided regarding antibiotic choices and dosing. Penicillin or amoxicillin remain the treatments of choice, and recommendations are made for the penicillin-allergic patient, which now include clindamycin.

Safety and immune responses in children after concurrent or sequential 2009 H1N1 and 2009-2010 seasonal trivalent influenza vaccinations.

BACKGROUND: Administering 2 separate vaccines for seasonal and pandemic influenza was necessary in 2009. Therefore, we conducted a randomized trial of monovalent 2009 H1N1 influenza vaccine (2009 H1N1 vaccine) and seasonal trivalent inactivated influenza vaccine (TIV; split virion) given sequentially or concurrently in previously vaccinated children. METHODS: Children randomized to 4 study groups and stratified by age received 1 dose of seasonal TIV and 2 doses of 2009 H1N1 vaccine in 1 of 4 combinations. Injections were given at 21-day intervals and serum samples for hemagglutination inhibition antibody responses were obtained prior to and 21 days after each vaccination. Reactogenicity and adverse events were monitored. RESULTS: All combinations of vaccines were safe in the 531 children enrolled. Generally, 1 dose of 2009 H1N1 vaccine and 1 dose of TIV, regardless of sequence or concurrency of administration, was immunogenic in children ≥ 10 years of age; children <10 years of age required 2 doses of 2009 H1N1 vaccine. CONCLUSIONS: Vaccines were generally well tolerated. The immune responses to 2009 H1N1 vaccine were adequate regardless of the sequence of vaccination in all age groups but the sequence affected titers to TIV antigens. Two doses of 2009 H1N1 vaccine were required to achieve a protective immune response in children <10 years of age. CLINICAL TRIALS REGISTRATION: NCT00943202.

Live and inactivated influenza vaccines induce similar humoral responses, but only live vaccines induce diverse T-cell responses in young children.

BACKGROUND: Two doses of either trivalent live attenuated or inactivated influenza vaccines (LAIV and TIV, respectively) are approved for young children (≥ 24 months old for LAIV and ≥ 6 months old for TIV) and induce protective antibody responses. However, whether combinations of LAIV and TIV are safe and equally immunogenic is unknown. Furthermore, LAIV is more protective than TIV in children for unclear reasons. METHODS: Children 6-35 months old were administered, 1 month apart, 2 doses of either TIV or LAIV, or combinations of LAIV and TIV in both prime/boost sequences. Influenza-specific antibodies were measured by hemagglutination inhibition (HAI), and T cells were studied in flow cytometric and functional assays. Highly conserved M1, M2, and NP peptides predicted to be presented by common HLA class I and II were used to stimulate interferon-γ enzyme-linked immunospot responses. RESULTS: All LAIV and/or TIV combinations were well tolerated and induced similar HAI responses. In contrast, only regimens containing LAIV induced influenza-specific CD4(+), CD8(+), and γδ T cells, including T cells specific for highly conserved influenza peptides. CONCLUSIONS: Prime/boost combinations of LAIV and TIV in young children were safe and induced similar protective antibodies. Only LAIV induced CD4(+), CD8(+), and γδ T cells relevant for broadly protective heterosubtypic immunity. CLINICAL TRIALS REGISTRATION: NCT00231907.

Physicians' opinions about critical attributes of a potential group A streptococcal vaccine.

A group A streptococcal (GAS) vaccine, while not currently available, offers the possibility of a more effective approach; however, barriers to its implementation are likely to exist. The objectives of this study were to describe the attitudes of physicians about the importance of preventing GAS-associated conditions and to identify potential barriers to vaccine implementation. Surveys were sent to randomly selected physicians from the AAP and the AAFP. The GAS conditions believed by respondents to be most important to prevent among pediatric patients were ARF (31%) followed by STSS (24%) and pharyngitis (20%). Pediatricians and family physicians identified similar factors that would encourage routine use of a GAS vaccine. Less than half of pediatricians and only a third of family physicians would recommend a GAS vaccine if it could not be given concurrently with other immunizations or if there were strong parental resistance to the vaccine. This descriptive study provides important information about the anticipated use of a GAS vaccine by primary care physicians in the United States.

Development of a patient-reported outcome measure for children with streptococcal pharyngitis.

OBJECTIVE: The objective of this study was to develop a patient-reported outcome measure (Strep-PRO) for assessing symptoms of group A Streptococcus (GAS) pharyngitis from the child's point of view and to present preliminary data on its internal reliability, construct validity, and responsiveness. METHODS: We selected 8 symptoms for inclusion in the Strep-PRO. We used the Strep-PRO to assess improvement in children who were aged 5 to 15 years and had confirmed GAS pharyngitis. Children completed the scale at study visits and as a diary at home. To evaluate internal reliability, we examined correlations between the items on the scale. To evaluate construct validity, we examined the correlation at entry between Strep-PRO scores and scores on other, previously validated measures of pain and functional status. To evaluate responsiveness, we examined the change in score from enrollment to follow-up. The correlation between the Strep-PRO score and parental assessment of symptoms was also evaluated. RESULTS: A total of 131 children were enrolled; 113 returned completed diaries. The internal reliability of the scale was high. The magnitude of correlations between Strep-PRO scores and other measures of pain and functional status ranged from 0.39 to 0.63. The responsiveness of the Strep-PRO was very good. The overall level of agreement between child Strep-PRO scores and parental assessment of symptoms was 0.57. CONCLUSIONS: The scale seems to measure effectively both pain and overall functional status in children with GAS pharyngitis. These data support the use of Strep-PRO as a measure of outcome in future clinical trials.

Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics.

Primary prevention of acute rheumatic fever is accomplished by proper identification and adequate antibiotic treatment of group A beta-hemolytic streptococcal (GAS) tonsillopharyngitis. Diagnosis of GAS pharyngitis is best accomplished by combining clinical judgment with diagnostic test results, the criterion standard of which is the throat culture. Penicillin (either oral penicillin V or injectable benzathine penicillin) is the treatment of choice, because it is cost-effective, has a narrow spectrum of activity, and has long-standing proven efficacy, and GAS resistant to penicillin have not been documented. For penicillin-allergic individuals, acceptable alternatives include a narrow-spectrum oral cephalosporin, oral clindamycin, or various oral macrolides or azalides. The individual who has had an attack of rheumatic fever is at very high risk of developing recurrences after subsequent GAS pharyngitis and needs continuous antimicrobial prophylaxis to prevent such recurrences (secondary prevention). The recommended duration of prophylaxis depends on the number of previous attacks, the time elapsed since the last attack, the risk of exposure to GAS infections, the age of the patient, and the presence or absence of cardiac involvement. Penicillin is again the agent of choice for secondary prophylaxis, but sulfadiazine or a macrolide or azalide are acceptable alternatives in penicillin-allergic individuals. This report updates the 1995 statement by the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee. It includes new recommendations for the diagnosis and treatment of GAS pharyngitis, as well as for the secondary prevention of rheumatic fever, and classifies the strength of the recommendations and level of evidence supporting them.

Peripheral neuropathy in an adolescent treated with linezolid.

The increased incidence of methicillin-resistant Staphyloccocus aureus infections may increase linezolid use in children. Peripheral neuropathy is a rare adverse effect of linezolid therapy and is more frequent with prolonged courses. We present an adolescent with peripheral neuropathy after 4 months of linezolid therapy and review the literature related to linezolid-induced neuropathies. Children receiving long-term linezolid therapy should be monitored for neuropathy.

Performance of a rapid antigen-detection test and throat culture in community pediatric offices: implications for management of pharyngitis.

OBJECTIVES: The goals were to establish performance characteristics of a rapid antigen-detection test and blood agar plate culture performed and interpreted in community pediatric offices and to assess the effect of the pretest likelihood of group A streptococcus pharyngitis on test performance (spectrum bias). METHODS: Two throat swabs were collected from 1848 children 3 to 18 years of age who were evaluated for acute pharyngitis between November 15, 2004, and May 15, 2005, in 6 community pediatric offices. One swab was used to perform the rapid antigen-detection test and a blood agar plate culture in the office and the other was sent to our laboratory for blood agar plate culture. Clinical findings were used to calculate the McIsaac score for each patient. The sensitivities of the office tests were calculated, with the hospital laboratory culture results as the criterion standard. RESULTS: Thirty percent of laboratory blood agar plate cultures yielded group A streptococcus (range among sites: 21%-36%). Rapid antigen-detection test sensitivity was 70% (range: 61%-80%). Office culture sensitivity was significantly greater, 81% (range: 71%-91%). Rapid antigen-detection test specificity was 98% (range: 98%-99.5%), and office culture specificity was 97% (range: 94%-99%), a difference that was not statistically significant. The sensitivity of a combined approach using the rapid antigen-detection test and back-up office culture was 85%. Among patients with McIsaac scores of >2, rapid antigen-detection test sensitivity was 78%, office culture sensitivity was 87%, and combined approach sensitivity was 91%. Positive diagnostic test results were significantly associated with McIsaac scores of >2. CONCLUSIONS: The sensitivity of the office culture was significantly greater than the sensitivity of the rapid antigen-detection test, but neither test was highly sensitive. The sensitivities of each diagnostic modality and the recommended combined approach were best among patients with greater pretest likelihood of group A streptococcus pharyngitis.

Safety and immunogenicity of trivalent inactivated influenza vaccine in infants.

BACKGROUND: Trivalent inactivated influenza vaccine (TIV) is not licensed for use in infants <6 months old, the group with the highest influenza hospitalization rates among children. METHODS: In this prospective, open-label study, 2 doses of TIV were administered to healthy infants aged 10-22 weeks. Adverse reactions were assessed, and hemagglutination inhibition (HAI) antibody titers were determined. Weekly telephone surveillance for influenza-like illness was conducted during the influenza season. RESULTS: A total of 42 infants were enrolled and completed the study. Mild local and systemic reactions were noted. In the first season (2004-2005), postvaccination HAI titers >1:32 were noted for 31.6%, 47.4%, and 21.1% of 19 subjects for H1N1, H3N2, and B strains included in the vaccine, respectively. In the second season (2005-2006), postvaccination HAI titers >1:32 were seen in 45.5%, 59.1%, and 0% of 23 subjects for H1N1, H3N2, and B strains included in the vaccine, respectively. Infants who were seronegative before vaccination (titers <1:8) were significantly more likely to have a 4-fold rise in antibody titer after vaccination, compared with infants who had prevaccination titers >1:8 (P<.001). CONCLUSION: Two doses of TIV were found to be safe and moderately immunogenic against some influenza strains. The presence of preexisting maternally derived antibody was associated with significantly lower seroresponse rates to vaccination. Whether vaccination with TIV will prevent influenza in these young children remains to be determined.

Effect of point-of-care influenza testing on management of febrile children.

OBJECTIVES: To determine the effect of point-of-care testing (POCT) for influenza on the physician management of febrile children who are at risk for serious bacterial illness (SBI) on the basis of age and temperature and who are presenting to a pediatric emergency department (ED) during an influenza outbreak. METHODS: Patients 2-3 months of age with temperature of > or = 38 degrees C and patients 3-24 months of age with temperature of > or = 39 degrees C who were presenting to a pediatric ED during an influenza outbreak were enrolled into a prospective, quasi-randomized, controlled trial. Influenza testing was performed on enrolled patients by either the POCT or the standard-testing (ST) methods. The two groups were compared in terms of laboratory testing, chest radiography, antibiotic use, visit-associated costs, pediatric ED lengths of stay, inpatient admission, and return visits to the pediatric ED. Similar analyses also were performed on the resulting subgroups of patients on the basis of method of testing (POCT or ST) and test result (positive or negative). RESULTS: Of 767 eligible patients, 700 (91%) completed the study. No significant differences were demonstrated between the POCT and ST groups with respect to laboratory tests ordered, chest radiographs obtained, antibiotic administration, inpatient admission, return visits to the pediatric ED, lengths of stay, or visit-associated costs. In the subgroup analysis, the adjusted odds ratios (ORs) for blood culture in influenza test-positive to -negative patients were 0.59 and 0.71 in the POCT and ST groups, respectively (p = 0.088). The adjusted ORs for urine culture in influenza test-positive to -negative patients were 0.46 and 0.67 in the POCT and ST groups, respectively (p = 0.005). CONCLUSIONS: When using a strategy of performing influenza testing on all patients at risk for SBI who presented to a pediatric ED during an influenza outbreak, the method of testing (POCT or ST) did not appear to significantly alter physician management, cost, or length of stay in the pediatric ED. However, if the interaction of the method of testing and the test result (positive or negative) were considered, a positive POCT for influenza was associated with a significant reduction in orders for urinalyses and urine cultures.

Clinicians' management of children and adolescents with acute pharyngitis.

OBJECTIVE: Sore throat is a common complaint in children and adolescents. With increasing antimicrobial resistance because of antimicrobial overuse, accurate diagnosis is imperative. Appropriate management of acute pharyngitis depends on proper use and interpretation of clinical findings, rapid antigen-detection tests, and throat cultures. We surveyed pediatricians and family physicians to evaluate their management strategies for children and adolescents with acute pharyngitis and to assess the availability and use of diagnostic tests in office practice. METHODS: In 2004, surveys were mailed to a random sample of 1000 pediatrician members of the American Academy of Pediatrics and 1000 family physician members of the American Academy of Family Physicians. We assessed factors associated with physicians using an appropriate management strategy for treating acute pharyngitis. RESULTS: Of 948 eligible responses, 42% of physicians would start antimicrobials before knowing diagnostic test results and continue them despite negative results, with 27% doing this often or always. When presented with clinical scenarios of patients with acute pharyngitis, < or =23% chose an empirical approach, 32% used an inappropriate strategy for a child with pharyngitis suggestive of group A Streptococcus, and 81% used an inappropriate strategy for a child with findings consistent with viral pharyngitis. Plating cultures in the office was associated with an appropriate management strategy, although not statistically significant. Solo/2-person practice and rural location were both independent factors predicting inappropriate strategies. CONCLUSIONS: There is much room for improvement in the management of acute pharyngitis in children and adolescents. Most physicians use appropriate management strategies; however, a substantial number uses inappropriate ones, particularly for children with likely viral pharyngitis. Efforts to help physicians improve practices will need to be multifaceted and should include health policy and educational approaches.

Varicella-related hospitalization and emergency department visit rates, before and after introduction of varicella vaccine, among white and black children in Hamilton County, Ohio.

OBJECTIVE: The American Academy of Pediatrics recommended routine use of varicella vaccine in pediatric practice in 1995. We examined the impact of varicella immunization on population-based rates of pediatric varicella-related hospitalizations and emergency department (ED) visits in the years before and after introduction of varicella vaccine. STUDY DESIGN: Discharge data for hospitalizations and ED encounters from 1990 through 2003 were queried for patients <20 years of age with varicella International Classification of Diseases, Ninth Revision, Clinical Modification codes (052.0-052.9) in any diagnostic position. Addresses were geocoded for identification of Hamilton County, Ohio, residents. Rates were calculated according to year, age, and race, with census estimates. RESULTS: During the 14-year study period, there were 3983 incident varicella cases; 335 patients were hospitalized and 3833 were treated only in the ED. The rate of varicella-related hospitalizations decreased from 15.7 cases per 100,000 population to 5.5 cases per 100,000 population between the prevaccine period (1990-1995) and the postvaccine period (1996-2003); varicella-related ED use decreased from 178.2 cases per 100,000 population to 61.2 cases per 100,000 population. In the prevaccine period, hospitalization and ED visit rates were significantly higher for black children than for white children. In the postvaccine period, hospitalization rates did not differ according to race but ED visit rates remained significantly higher for black children, compared with white children. CONCLUSIONS: Varicella-related hospitalization and ED visit rates decreased significantly for both white and black children in Hamilton County, Ohio, after the introduction of varicella vaccine, and the racial disparity found before licensure decreased after licensure.

Vulvar ulcers in young females: a manifestation of aphthosis.

STUDY OBJECTIVE: To examine the etiology, clinical course, and outcomes of non-sexually transmitted vulvar ulcers in young females. DESIGN: A prospective cohort study of subjects referred to a tertiary center who had active vulvar ulcers and no evidence of sexually transmitted infections were evaluated with a structured clinical and laboratory protocol and followed with visits or telephone calls. RESULTS: Twenty eligible subjects had a mean age of 14 years (range 10-19), and five were premenarchal. Nineteen reported systemic symptoms such as fever, malaise, and headache. Most ulcers were >1cm in diameter (range 0.3-5 cm) and were located on the medial aspect of the labia minora. All viral, bacterial, and fungal cultures were negative. Serologic testing for Epstein-Barr virus (EBV) infection demonstrated 10 subjects with evidence of prior infection, two with acute infection, one indeterminate, and seven negative for infection. Two subjects had evidence of possible acute cytomegalovirus (CMV) infection. Other laboratory findings were nonspecific. The median duration of pain was 10 days (range 6-30), and 75% healed by 21 days. Follow up was available for 19 subjects (median 14 months). Seven experienced recurrent ulcers 2-16 months after the initial episode, and 10 had experienced oral aphthous ulcers. None met criteria for other etiologies of vulvar ulcers reported in the literature. CONCLUSIONS: No single infectious agent was identified as a cause of vulvar ulcers. Most cases were not temporally associated with either acute EBV or CMV infection. These ulcers are consistent with aphthous major or complex aphthosis that arise in response to acute illness.