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Objective. Neuropsychological functioning and its correlation with viral load were investigated for previously treated HIV-infected children who underwent a change in treatment regimen. Methods. Thirteen age-appropriate measures of cognitive, neurologic, and behavioral functioning were administered to 489 HIV-infected children who were aged 4 months to 17 years and had been treated previously for at least 16 weeks with antiretroviral therapy. These clinically and immunologically stable children were randomized onto I of 7 drug treatment combinations, 6 of which included a protease inhibitor (PI), and evaluated prospectively for 48 weeks with respect to changes in neuropsychological performance and viral load. Results. Neuropsychological functioning was significantly poorer at baseline for the HIV-infected children as compared with established norms for their age. Children with higher viral load had poorer cognitive, both-hands fine-motor, and neurologic signs at baseline, but single-hand fine-motor and behavioral functioning were not correlated with viral load. After 48 weeks of treatment with PI-containing combination therapy, there was significant improvement in only the vocabulary score. Neuropsychological changes did not differ among the 6 PI-containing combination regimens. At week 48, even children with a viral load response below the level of detection (RNA [less than or equal to] 400 copies/mL) still showed poorer neuropsychological functioning compared with established norms. Conclusion. Poor neuropsychological functioning was seen for HIV-infected children and was worse for children with higher viral loads. Only 1 measure of neuropsychological functioning showed improvement after treatment with Pl-containing combination therapy, and the extent of that improvement was relatively minor. Treatment strategies for children with HIV disease need to be reevaluated so that they consider restoration of neuropsychological functioning in addition to lowering the viral load. Pediatrics 2005;115:380-387; HIV, child, neuropsychological tests, cognitive science, neurologic examination, behavior, antiretroviral agents, protease inhibitors., ABBREVIATIONS. CNS, central nervous system; NP, neuropsychological; ZDV, zidovudine; ddl, didanosine; Pl, protease inhibitor; PACTG, Pediatric AIDS Clinical Trials Group; CDC, Centers for Disease Control and Prevention; NRTI, nucleoside reverse [...]

Objective. Despite immunization with heptavalent pneumococcal conjugate vaccine (PCV7), the rising prevalence of antibiotic resistance makes Streptococcus pneumoniae a continuing threat to child health. Data on carriage of resistant organisms by healthy children in communities in which immunization with PCV7 has been implemented will help to define and decrease these risks further. Methods. Children who were Results. S pneumoniae was isolated from the nasopharynx of 190 (26%) of the 742 children studied. Of the 166 tested, 33% were nonsusceptible to penicillin, with 14% showing intermediate susceptibility (minimum inhibitory concentration [MIC] 0.12-1.0) and 19% fully resistant (MIC [greater than or equal to] 2). Nonsusceptibility to other antibiotics was common, including ceftriaxone (14%), erythromycin (22%), and trimethoprim/sulfa (31%); 20% of S pneumoniae isolates were not susceptible to [greater than or equal to] 3 antibiotics. Thirty-six percent of isolates were of serotypes covered by PCV7; 30% were of PCV7 serogroups and potentially cross-reactive, but not 1 of the 7 included serotypes; and 34% were unrelated to PCV7 serogroups. Nonsusceptibility to penicillin was more common in PCV7-included strains (45%) and potentially cross-reactive strains (51%) than in non-PCV7 serotypes (8%). Risk factors for PNSP colonization included child care attendance (odds ratio [OR]: 3.9; 95% confidence interval [CI]: 2.3-6.5), current respiratory tract infection (OR: 4.7; 95% CI 2.5-8.6), and recent antibiotic use (OR: 1.7; 95% CI: 1.0-2.8). PCV7 immunization was associated with decreased carriage of PCV7-included serotypes but not with an overall decrease in S pneumoniae colonization or with a decline in PNSP colonization. Conclusions. In this multicommunity sample, pneumococcal antibiotic resistance was common and was most frequently found in PCV7-included and PCV7 serogroup strains. The long-term impact of PCV7 immunization will be partially determined by the protection that it affords against invasive infection with potentially cross-reactive serotypes, as well as the virulence and future resistance patterns of unrelated serotypes. Pediatrics 2003;112:862-869; antibiotic resistance, penicillin resistance, Streptococcus pneumoniae, nasopharyngeal carriage., ABBREVIATIONS. PNSP, penicillin nonsusceptible Streptococcus pneumoniae; MDR, multidrug resistance; PCV7, heptavalent pneumococcal conjugate vaccine; RTI, respiratory tract infection; OR, odds ratio; CI, confidence interval. The rising prevalence of antibiotic-resistant bacterial [...]

Seven-valent pneumococcal conjugate vaccine (PCV7) was licensed in February 2000. In June 2000, the Advisory Committee on Immunization Practices and the American Academy of Pediatrics recommended the universal administration of pneumococcal conjugate vaccine for all children 23 months of age and younger and for children 24 to 59 months of age who are at high risk for serious pneumococcal disease. Since then, > 23 million doses have been administered in the United States. Postlicensure surveillance of invasive pneumococcal disease (IPD) in the United States from the Active Bacterial Core Surveillance program at the Centers for Disease Control and Prevention and the Northern California Kaiser Permanente Vaccine Study Center has reported a decline in IPD and in pneumococcal disease incidence as a result of vaccine serotypes, respectively. During this period, issues critical to the long-term success of PCV7 have become more relevant: Will PCV7 be as effective in groups of children who are at high risk for IPD as in healthy children? Will nonvaccine types replace vaccine serotypes in the nasopharynx and in disease? Why are the results of the clinical trials different for IPD and for acute otitis media? How many doses of PCV7 and what concentrations of antibody are necessary for protection? Will universal administration of PCV7 to children younger than 2 years reduce antimicrobial drug resistance and alter prescribing patterns of physicians for febrile infants? Have there been unanticipated adverse events or benefits observed? The purpose of this report is to review the current data available to address these questions and to identify gaps that will require additional knowledge to determine the ultimate value of pneumococcal conjugate vaccines in reducing the burden of pneumococcal disease in infants and children. Pediatrics 2002;110:805-814; pneumococcal disease, pneumococcal vaccine, conjugate vaccine, carriage, serotypes., ABBREVIATIONS. PCV, pneumococcal conjugate vaccine; IPD, invasive pneumococcal disease; NCKP, Northern California Kaiser Permanente; HIV, human immunodeficiency virus; NP, nasopharyngeal; PPV, pneumococcal polysaccharide vaccine; ELISA, enzyme-linked immunosorbent assay; OPA, opsonophagocytic [...]

The incidence of syphilis among women delivering babies at the Boston City Hospital appeared to increase from 1951 to 1991. Blood samples from 647 women admitted for delivery were tested for syphilis in 1991. These results were compared with those from 1,005 women tested after delivery in 1951. In the earlier study 2.4% of the women tested positive for syphilis either before or during pregnancy. In the 1991 study, 3.9% of the women tested positive for syphilis during pregnancy or delivery. In the 1991 study women who tested positive were more likely to be infected with other sexually transmitted diseases and more likely to use illicit drugs. No cases of congenital syphilis were diagnosed in either study., Objective. To examine the incidence and epidemiologic correlates of congenital syphilis at an inner-city Boston hospital, and draw comparisons with the situation at the same hospital 40 years ago. Design. Chart review and comparison with data collected in 1951. Setting. Maternity and pediatric services at Boston City Hospital. Methods. A study conducted in 1951 on the maternity service of Boston City Hospital in which demographic data were collected on all women admitted in labor over a 5-month period was replicated. Serologic testing for syphilis was carried out on these women, and the demographic and medical correlates of positive maternal syphilis serology were examined. This study was repeated exactly 40 years later, using the cord blood screening for syphilis done routinely at delivery and a review of prenatal records. Results. From a group made up largely of married white women in 1951, the study population shifted in 1991 to a group made up mostly of minority women, with 75% unmarried. In 1951, 24 patients were diagnosed with syphilis either before or during the pregnancy, giving a prevalence rate of 2.4%. In 1991, 25 of 647 women were diagnosed with syphilis, for a prevalence rate of 3.9%. The women with positive cord blood serologies had a higher rate of other sexually transmitted diseases and substance abuse. No symptomatic cases of congenital syphilis were seen in 1951 or in 1991, although at least 11 of the 26 infants born to mothers with positive serologies in 1991 received intravenous penicillin therapy. Conclusions. The continued prevalence of diagnosed syphilis in women at delivery reflects an inner-city epidemic of congenital syphilis that is tied to substance abuse, human immunodeficiency virus, and changing social patterns, as well to older problems of serologic screening, prenatal care, treatment failures, and maternal reinfection. It is essential that screening programs be maintained and improved in this high-risk population, and that infants born to mothers with positive serologies receive full and adequate treatment if there is any doubt at all about their infection status. Pediatrics 1994;94: 24-28; syphilis, congenital; serologic tests, prenatal screening, epidemiology, history.

To the Editor.-- The article by Levine and colleagues[1] entitled "Risk Factors for Invasive Pneumococcal Disease in Children: A Population-Based Case-Control Study in North America" that appeared in the March [...]

ABBREVIATIONS. IPD, invasive pneumococcal disease; PCV7, 7-valent pneumococcal conjugate vaccine; NVST, nonvaccine serotype; VSG, vaccine serogroup., The decline in invasive pneumococcal disease (IPD) as reported by Kaplan et al (1) confirms the strategy of linking capsular polysaccharide (type-specific carbohydrate) to a protein carrier to enhance immunogenicity [...]

A criticism of practice guidelines for treating feverish children may be as extreme as the guidelines themselves. The guidelines recommend aggressively testing and treating all feverish children who have an elevated white blood cell count. They are based on a 1975 study which found that elevated temperature and white blood cell count predicted which children had serious bacterial infections. Critics of the guidelines say such aggressive testing and treatment is unnecessary and expensive. The best treatment for these children may lie somewhere between these two extremes., In 1975, Teele and colleagues[1] identified the risk factors for and occurrence of bacteremia in young febrile children presenting to a pediatric walk-in clinic. They found that 3.2% of children [...]

Objective. The introduction of heptavalent conjugate pneumococcal vaccine (PCV7) has raised concerns for replacement with nonvaccine serotypes in both invasive disease and asymptomatic carriage. Analysis of colonizing serotypes among healthy children in the community provides critical data on such changes. Methods. Nasopharyngeal specimens were obtained from children who were younger than 7 years during well-child or sick visits in primary care practices in 16 Massachusetts communities during 2001 and 2004. Susceptibility testing and serotyping were performed on isolated Streptococcus pneumoniae strains. Vaccination history with PCV7 was abstracted from the medical record. Results. Among colonizing pneumococcal isolates, PCV7 serotypes decreased from 36% to 14%, and non-PCV7 serotypes increased from 34% to 55%. Overall carriage did not change (26% to 23%); neither did carriage of potentially cross-reactive serotypes (30% to 31%). The most common non-PCV7 serotypes were serotypes 11,15, and 29. There was a substantial increase in penicillin nonsusceptibility from 8% to 25% in non-PCV7 serotypes; 35% were highly resistant to penicillin. Penicillin nonsusceptibility increased from 45% to 56% among PCV7 serotypes while remaining stable among PCV7 potentially cross-reactive strains (51% vs 54%). Conclusions. Pneumococcal colonization has changed after the introduction of PCV7, both in serotype distribution and in patterns of antibiotic resistance. The frequency of nonvaccine strains has increased, and the proportion of nonvaccine isolates that are not susceptible to penicillin has tripled. This shift toward increased carriage of nonvaccine serotypes warrants vigilance for changes in the epidemiology of invasive pneumococcal disease. Pediatrics 2005;116:e408-e413. URL: www. pediatrics.org/cgi/doi/10.1542/peds.2004-2338; Streptococcus pneumoniae, pneumococcal conjugate vaccine, antibiotic resistance, colonization., Susan S. Huang, MD, MPH; Richard Platt, MD; Sheryl L. Rifas-Shiman, MPH; Stephen I. Pelton, MD; Donald Goldmarm, MD; and Jonathan A. Finkelstein, MD, [...]

Pediatricians frequently feel pressure to prescribe antibiotics to sick children who do not need them. The overuse of antibiotics contributes to the development of drug-resistant organisms. Researchers surveyed 610 practicing pediatricians, and found that 96% had been asked by parents for antibiotic drugs when they were not needed, such as when the child had a viral infection that would not respond to antibiotics. Forty percent of surveyed doctors reported 10 or more such requests in the previous month. One-third of doctors occasionally or more frequently provided the drugs, even though they were not indicated. Parental education, the doctors believe, would best reduce these requests., Background. Emergence of resistant bacterial pathogens has increased concerns about antibiotic prescribing patterns. Parent expectations and pressure may influence these patterns. Objective. To understand how parents influence the prescribing patterns of physicians and what strategies physicians believe are important if we are going to reduce inappropriate use of oral antimicrobial agents. Designs and Methods. One thousand pediatricians who are members of the American Academy of Pediatrics were asked to complete a semi-structured questionnaire. The physicians were chosen randomly by the American Academy of Pediatrics. Results. Nine hundred fifteen pediatricians were eligible and 610 surveys were analyzable, for a response rate of 67%. The majority of respondents were male (56%), worked in a group practice (51%), saw an average of 114 patients per week and were in practice for 14 years. Forty percent of the pediatricians indicated that 10 or more times in the past month a parent had requested an antibiotic when the physician did not feel it was indicated. Forty-eight percent reported that parents always, most of the time, or often pressure them to prescribe antibiotics when their children are ill but antibiotics are not indicated. In follow-up questions, approximately one-third of physicians reported they occasionally or more frequently comply with these requests. Seventy-eight percent felt that educating parents would be the single most important program for reducing inappropriate oral antibiotic use and 54% indicated that parental pressure, in contrast to concerns about legal liability (12%) or need to be efficient in practice (19%), contributed most to inappropriate use of oral antibiotics. Conclusions. Pediatricians acknowledge prescribing antimicrobial agents when they are not indicated. Pediatricians believe educating parents is necessary to promote the judicious use of antimicrobial agents. Pediatrics 1999;103:395--401; antibiotics, antimicrobials, parents, pediatricians., ABBREVIATIONS. AOM, acute otitis media; AAP, American Academy of Pediatrics. Over the past decade, decreasing susceptibility of Streptococcus pneumoniae to antimicrobial agents has been increasingly reported around the world.[1-3] S [...]

Objective: To examine whether there is a different clinical profile and severity of invasive pneumococcal disease (IPD) in children caused by nonvaccine types in the era of 13-valent pneumococcal conjugate vaccine (PCV13)., Methods: Observational study of childhood IPD in Massachusetts based on state public health surveillance data comparing pre-PCV13 (2007-2009) and post-PCV13 (2010-2012) eras., Results: There were 168 pre-PCV13 cases of IPD and 85 post-PCV13 cases of IPD in Massachusetts children ≤5 years of age. PCV13 serotypes declined by 18% in the first 2 years after PCV13 use (P = .011). In the post-PCV13 phase, a higher proportion of children were hospitalized (57.6% vs. 50.6%), and a higher proportion of children had comorbidity (23.5% vs. 19.6%). Neither difference was statistically significant, nor were comparisons of IPD caused by vaccine and nonvaccine types. Children with comorbidities had higher rates of IPD caused by a nonvaccine type (27.6% vs. 17.2%; P = .085), were more likely to be hospitalized (80.4% vs. 50%; P < .0001), and were more likely to have a longer hospital stay (median of 3 days vs. 0.5 days; P = .0001)., Conclusions: Initial data suggest that nonvaccine serotypes are more common in children with underlying conditions, who have greater morbidity from disease. In the post-PCV13 era, a larger proportion of patients are hospitalized, but mortality rates are unchanged. Routine vaccination with PCV13 may not be enough to reduce the risk in patients with comorbidity., (Copyright © 2014 by the American Academy of Pediatrics.)

Objectives: The goals were to assess serial changes in Streptococcus pneumoniae serotypes and antibiotic resistance in young children and to evaluate whether risk factors for carriage have been altered by heptavalent pneumococcal conjugate vaccine (PCV7)., Methods: Nasopharyngeal specimens and questionnaire/medical record data were obtained from children 3 months to <7 years of age in primary care practices in 16 Massachusetts communities during the winter seasons of 2000-2001 and 2003-2004 and in 8 communities in 2006-2007. Antimicrobial susceptibility testing and serotyping were performed with S pneumoniae isolates., Results: We collected 678, 988, and 972 specimens during the sampling periods in 2000-2001, 2003-2004, and 2006-2007, respectively. Carriage of non-PCV7 serotypes increased from 15% to 19% and 29% (P < .001), with vaccine serotypes decreasing to 3% of carried serotypes in 2006-2007. The relative contribution of several non-PCV7 serotypes, including 19A, 35B, and 23A, increased across sampling periods. By 2007, commonly carried serotypes included 19A (16%), 6A (12%), 15B/C (11%), 35B (9%), and 11A (8%), and high-prevalence serotypes seemed to have greater proportions of penicillin nonsusceptibility. In multivariate models, common predictors of pneumococcal carriage, such as child care attendance, upper respiratory tract infection, and the presence of young siblings, persisted., Conclusions: The virtual disappearance of vaccine serotypes in S pneumoniae carriage has occurred in young children, with rapid replacement with penicillin-nonsusceptible nonvaccine serotypes, particularly 19A and 35B. Except for the age group at highest risk, previous predictors of carriage, such as child care attendance and the presence of young siblings, have not been changed by the vaccine.

Objective: Our goal was to evaluate the immunogenicity and safety of pertussis booster vaccination in children infected with HIV on highly active antiretroviral therapy (HAART)., Patients and Methods: HIV-infected children on stable HAART for > or = 3 months with plasma HIV-RNA concentrations of < 30,000 to 60,000 copies per mL who previously received > or = 4 doses of diphtheria-tetanus-pertussis (DTP)-containing vaccine were eligible. Diphtheria-tetanus-acellular pertussis (DTaP) vaccine was administered to subjects 2 to < 7 years old who had 4 previous DTP-containing vaccines, subjects 2 to < 7 years old who had > or = 5 previous DTP-containing vaccines and negative tetanus antibody, and subjects > or = 7 to < or = 13 years old who had negative tetanus antibody. Pertussis toxin and filamentous hemagglutinin antibodies were measured before and 8, 24, and 72 weeks after DTaP vaccine., Results: Ninety-two subjects received DTaP vaccine and met criteria for analysis. Antibody concentrations were low at entry: pertussis toxin geometric mean concentration at 4.8 enzyme-linked immunosorbent assay units (EU) per mL and filamentous hemagglutinin geometric mean concentration at 4.1 EU/mL. Pertussis toxin and filamentous hemagglutinin geometric mean concentrations rose to 22.3 and 77.0 EU/mL, respectively, 8 weeks after the study DTaP vaccine. Antibody concentrations fell by 24 weeks after vaccination but remained higher than before vaccination. Predictors of response 8 weeks after DTaP vaccine included the concentration of homologous antibody, lower HIV-RNA level, and higher CD4 percentage at entry. One vaccinated subject experienced erythema and induration of > or = 25 mm., Conclusions: A DTaP vaccine booster was well tolerated by children on HAART and induced increases in antibodies. Antibody concentrations after vaccination were lower than those reported in populations uninfected by HIV. Although comparison among studies must be made with caution, these data suggest that children infected with HIV may be deficient in immunologic memory from previous DTP-containing vaccination and/or that immune reconstitution with HAART may be incomplete for pertussis antigens.