The Pediatric Infectious Disease Journal

Published by Lippincott, Williams & Wilkins
Online ISSN: 1532-0987
Print ISSN: 0891-3668
Publications
The objective of this article is to review the literature related to ciprofloxacin 0.3% and dexamethasone 0.1% sterile otic suspension. A systematic literature search utilizing Medline was conducted to identify peer-reviewed articles related to safety and efficacy. A total of 47 publications were identified and reviewed herein. The literature supports the use of antibiotic/antiiflammatory combination ear drops in the treatment of both acute otitis externa and acute otitis media in pediatric patients with tympanostomy tubes. Ciprofloxacin/dexamethasone has been demonstrated as safe and effective with regard to clinical cures and microbiological eradication of pathogens in either disease with low treatment failure rates. Additionally, the literature also provides clear evidence for the contribution of dexamethasone when added to ciprofloxacin for the topical treatment of ear infections.
 
The purpose of the study was to compare the efficacy of 10% povidone-iodine with that of 0.5% chlorhexidine gluconate in 70% isopropyl alcohol for the prevention of peripheral intravenous catheter colonization in neonates. This was a multicenter, nonrandomized prospective study in a tertiary neonatal intensive care setting in which povidone-iodine and chlorhexidine gluconate were each used as antiseptic skin preparations over sequential 6-month periods. During the first 6 months of the study when povidone-iodine was in use 9.3% (38 of 408) of catheters were colonized. During the second 6 months of the study when chlorhexidine gluconate was in use, catheter colonization occurred in 4.7% (20 of 418, P = 0.01). Catheter-related bacteremia occurred during only 0.2% (2 of 826) of all catheterizations. Heavy skin colonization before catheter insertion (relative risk, 3.6; 95% confidence interval, 1.9, 7.0), catheterization > or = 72 hours (relative risk. 2.0; 95% confidence interval, 1.01, 3.8) and gestational age < or = 32 weeks (relative risk, 1.8; 95% confidence interval, 1.02, 3.3) increased colonization risk. Ampicillin infusion (relative risk, 0.4; 95% confidence interval, 0.2, 0.7) and 0.5% chlorhexidine gluconate cutaneous antisepsis (relative risk, 0.4; 95% confidence interval, 0.2, 0.8) were factors associated with decreased colonization risk. We conclude that 0.5% chlorhexidine gluconate in 70% isopropyl alcohol appears to be more efficacious than 10% povidone-iodine for the prevention of peripheral intravenous catheter colonization in neonates.
 
Two previously healthy children developed Clostridium difficile ribotype 027-associated disease concomitantly with norovirus infection. Viral gastroenteritis may contribute to epithelial homeostasis of the intestine and exacerbate the effects of toxins produced by C. difficile ribotype 027.
 
In adults, HLA haplotype B8-DRB1*03 is clearly associated with a severe clinical course of nephropathia epidemica caused by Puumala hantavirus. We investigated whether the same applies in pediatric patients. This HLA haplotype was found in 20 of 39 (51%) of the patients, a significantly higher figure than in the Finnish population (19%). There were, however, no significant differences in the clinical picture between patients with and without HLA B8-DRB1*03.
 
Reports of long-term tenofovir disoproxil fumarate (TDF) treatment in HIV-infected adolescents are limited. We present final results from the open-label (OL) TDF extension following the randomized, placebo-controlled, double-blind phase of GS-US-104-0321(Study 321). HIV-infected 12-17 year-olds failing antiretrovirals who received TDF 300 mg or placebo (PBO) with an optimized background regimen (OBR) for 24-48 weeks received OL TDF plus OBR in a single arm study extension. HIV-1 RNA and safety, including bone mineral density (BMD), was assessed in all TDF recipients. 81 subjects received TDF (median duration 96 weeks). No subject died or discontinued OL TDF for safety/tolerability. At Week 144, proportions with HIV-1 RNA <50 copies/mL were 30.4% (7/23 subjects with baseline HIV-1 RNA>1000 c/mL initially randomized to TDF), 41.7% (5/12 subjects with HIV-1 RNA < 1000 c/mL who switched PBO to TDF), and 0% (0/2 subjects failed randomized PBO plus OBR with HIV-1 RNA>1000 c/mL and switched PBO to TDF). Viral resistance to TDF occurred in 1 subject. At Week 144, median decrease in estimated GFR (eGFR) was 38.1 mL/min/1.73 m2 (n=25). Increases in median spine (+12.70%, n=26) and total body less head (TBLH) BMD (+4.32%, n=26) and height-age adjusted Z-scores (n=21; +0.457 for spine, +0.152 for TBLH) were observed at Week 144. Five of 81 subjects (6%) had persistent >4% BMD decreases from baseline. Despite suboptimal adherence, some subjects had virologic responses to TDF plus OBR, and TDF resistance was rare. TDF was well-tolerated and can be considered for treatment of HIV-infected adolescents.
 
Comparison of the clinical features of H1N1/09 and previous years' influenza A cases reveals that, in children presenting with severe disease, H1N1/09 influenza is associated with an increased prevalence of shock, duration of admission, and mortality. This was not attributable to demographic differences or underlying disease. H1N1/09 influenza is associated with more severe diseases than those with previous years' influenza A strains.
 
Purulent bacterial conjunctivitis affects all ages with high frequency in newborns and children. In a subset of 150 children included in a large study having enrolled 1043 patients, our aim was to analyze in children, the efficacy and safety of azithromycin 1.5% eye-drops in the treatment of this disease. This multicenter, randomized, investigator-masked, parallel-group study, included 150 children and adolescents to study safety and compare azithromycin 1.5% eye drops twice daily for 3 days and tobramycin 0.3% 1 drop every 2 hours for 2 days then 4 times daily for 5 days. Out of 150 patients included, 58 had positive cultures and were studied for efficacy. Signs and symptoms were evaluated and cultures obtained at baseline, Days 3 and 9. Primary efficacy variable was the clinical cure (score 0 for bulbar conjunctival injection and purulent discharge) at the test of cure visit (day 9). Both treatments were effective with a clinical and microbiologic cure of more than 80% of children on day 9. Azithromycin therapy provided a greater bacteriologic cure on day 3 than did tobramycin (P < 0.001) and eradicated bacteria that were defined as resistant, using classical antibiogram. No adverse effects were noted on the ocular surface. Azithromycin 1.5% eye drops leads to a rapid clinical and microbiological cure.
 
Colonization with Candida spp. is an important risk factor for systemic infection in very low birth weight (VLBW; <1500 g) and extremely low birth weight (ELBW, <1000 g) infants. ELBW infants are at a higher risk than VLBW infants for fungal sepsis and its associated mortality, but few studies have examined fungal colonization exclusively in ELBW infants. Fungal colonization data were analyzed retrospectively in 50 high risk ELBW infants. Weekly surveillance fungal cultures of the skin, gastrointestinal tract, respiratory tract and umbilicus had been performed from birth through the first 6 weeks of life. Colonization was analyzed for time of initial colonization, site, species and spread of Candida from one site to another. Candida was isolated from surveillance cultures in 31 of 50 (62%) infants. Colonization was inversely proportional to gestational age. Initial week of both the fungal colonization of the skin [1 (0-6) week, median (range)] and gastrointestinal tract [2 (0-6)] preceded colonization of the respiratory tract [3 (1-6)] (P = 0.0001). Among infants colonized by only 1 of the species, colonization at 2 or more sites occurred similarly with Candida albicans (77%) and Candida parapsilosis (85%), whereas colonization at 3 or more sites occurred more frequently with C. albicans (69%) compared with C. parapsilosis (23%) (P = 0.047). Fungal colonization occurs on the skin and gastrointestinal tract before the respiratory tract. In addition, C. albicans is more likely than C. parapsilosis to colonize multiple sites.
 
One hundred two children, 45 days to 14 years of age, with proven brucellosis were studied to illustrate the epidemiologic, clinical and laboratory findings and to assess the outcome of antimicrobial therapy. The main source of infection was the consumption of raw milk in 80% of the patients. The predominant presenting symptoms and signs were fever, arthralgia, malaise, weight loss, arthritis, hepatosplenomegaly and lymphadenopathy. Brucella melitensis was isolated from 75% of 87 patients. Diverse hematologic and biochemical abnormalities were found. Different durations and combinations of trimethoprim-sulfamethoxazole or tetracycline plus streptomycin or rifampin were used for therapy. Eight-five patients were followed for an average of 14 months. Twelve (85.7%) of 14 patients treated with two-antibiotic combinations for 3 weeks relapsed, as did 5 (8%) of 62 patients treated for at least 6 weeks (P less than 0.001). No relapses occurred in 9 patients treated with trimethoprim-sulfamethoxazole and rifampin for 8 to 12 weeks plus streptomycin for the first 3 weeks. Longer duration and combination of antibiotic therapy seem warranted to improve outcome and to prevent relapses.
 
Live oral cholera vaccine CVD 103-HgR is well-tolerated and immunogenic when administered to adults, school age children and preschool children in a single 5 x 10(9) colony-forming unit dose. Because elicitation of immune responses after administration of a single dose is exceptional for any oral vaccine in any age group, CVD 103-HgR was used as a probe to investigate the clinical acceptability, practicality and immunogenicity of this vaccine in infants and toddlers 3 to 17 months of age. The study was undertaken successively in 12- to 17-month-olds (n = 104), 7- to 11-month-olds (n = 106) and 3- to 5-month-olds (n = 102). One-half of the subjects were randomly allocated to receive vaccine and the other one-half to receive placebo, in double blind fashion. After 2 weeks of double blind follow-up, all subjects received a dose of vaccine. Vibriocidal antibody titers were measured on coded sera collected at baseline and 2 weeks after each dosing. The buffered vaccine "cocktail" had a volume of 100 ml; subjects who ingested > or =70 ml were considered fully vaccinated. Only 37% of subjects overall (25% of 3- to 5-month-olds) ingested > or =70 ml of the cocktail. The vaccine was well-tolerated with no significant differences in the rate or severity of adverse reactions after ingestion of vaccine vs. placebo. Seroconversion after ingestion of a single dose of CVD 103-HgR was similar in fully vaccinated subjects (66%) and in those who ingested a smaller fraction of the vaccine cocktail (63%). Of subjects who ingested two doses, 5 of 118 excreted vaccine organisms on Day 7 after the first dose vs. 0 of 118 after the second dose. Single dose oral CVD 103-HgR is well-tolerated and immunogenic in infants even when a partial dose is ingested. The buffered vaccine cocktail that is readily imbibed by older children is not appealing to young infants, and improved vaccine formulations and delivery vehicles for immunizing infants must be sought.
 
A combined immunization strategy for administration of human papillomavirus (HPV) vaccine with other routine vaccines may lead to better compliance. Reactions and immunologic interference with concomitantly administered vaccines are unpredictable, necessitating clinical evaluation. This was a randomized, open study conducted at 48 centers in the United States (NCT00369824). Healthy girls 11 to 18 years of age were randomized equally to 1 of 6 groups to receive 3 doses of HPV-16/18 AS04-adjuvanted vaccine administered at 0, 1, and 6 or 1, 2, and 7 months, with or without 1 dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) and/or 1 dose of meningococcal polysaccharide diphtheria toxoid conjugate vaccine (MCV4) in different coadministration regimens (1283 girls vaccinated). Coadministered vaccines were injected at separate sites. Antibodies were measured for all vaccine components. Reactogenicity and safety were monitored. The prespecified criteria for noninferiority were met for all primary and secondary immunogenicity end points, demonstrating similar immunogenicity of Tdap and MCV4 when given alone or coadministered with the HPV vaccine. Immunogenicity of the HPV vaccine (in terms of seroconversion rates and geometric mean antibody titers to HPV antigens) was similar, regardless of whether it was given alone or coadministered with Tdap and/or MCV4. No differences were observed in the reactogenicity profile of the HPV vaccine administered alone or coadministered with either Tdap and/or MCV4 in different regimens. Concomitant administration of HPV-16/18 AS04-adjuvanted vaccine with Tdap and/or MCV4 in different regimens did not interfere with the immune response to any of the vaccines and had an acceptable safety profile.
 
GARDASIL/SILGARD is a quadrivalent human papillomavirus (HPV) vaccine with activity against HPV 6/11/16/18. In many countries, GARDASIL is recommended for routine use among adolescents at the same age as other vaccines. In this study, we evaluated the immunogenicity and safety of GARDASIL administered concomitantly with REPEVAX (diphtheria, tetanus, acellular pertussis, and poliomyelitis vaccine). This was an open-label, randomized, multicenter study. We enrolled males (n = 260) and females (n = 583) aged 11 to 17 years. All subjects received a 0.5 mL dose of GARDASIL at day 1, month 2, and month 6, and a 0.5 mL dose of REPEVAX either on day 1 (opposite limb from GARDASIL) or at month 1. Antibody levels for all vaccine components were measured. We monitored systemic and injection-site adverse experiences (AEs) and serious adverse experiences. Immune response for all GARDASIL antigens following concomitant administration of the vaccines was demonstrated noninferior to nonconcomitant administration. Seroconversion for HPV 6, 11, 16, and 18 was >99.7% in both concomitant and nonconcomitant vaccination groups. For REPEVAX, noninferiority of immune response was established for diphtheria, tetanus, and all polio and pertussis antigens. Concomitant administration of the 2 vaccines was generally well-tolerated, although there was a small increase in headache and injection-site swelling in the concomitant group. Overall, concomitant administration of GARDASIL and REPEVAX was generally well-tolerated and did not interfere with the immune response to either vaccine. Concomitant administration of vaccines would minimize the number of visits required to deliver each vaccine individually.
 
Background: This study evaluated the immunogenicity, reactogenicity and safety of the combined Haemophilus influenzae type B Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) coadministered with diphtheria, tetanus, acellular pertussis hepatitis B-inactivated poliovirus (DTPa-HBV-IPV) as 2 primary and 1 booster doses at 3, 5 and 11 months of age. Methods: In this phase III open study (NCT00327184), 709 infants were randomized in 2 parallel groups (1:1) to receive either Hib-MenC-TT coadministered with DTPa-HBV-IPV or control vaccines (MenC-TT coadministered with DTPa-HBV-IPV/Hib). Serum bactericidal activity for MenC (rSBA-MenC) and antibody concentrations against polyribosylribitol phosphate from Hib (anti-PRP) and hepatitis B (anti-HBs) were measured at 1 month after dose 2, before booster and 1 month after booster dose. Solicited (local/general) and unsolicited symptoms were assessed up to 4 and 31 days, respectively, after each vaccination. Serious adverse events were recorded throughout the study. Results: One month after dose 2, high percentages of infants in both groups had rSBA-MenC titers ≥ 8 (≥ 99.1%), anti-PRP concentrations ≥ 0.15 μg/mL (≥ 96.5%) and anti-HBs concentrations ≥ 10 mIU/mL (≥ 95.3%), which persisted up to the booster vaccination (≥ 94.5%, ≥ 86.1%, ≥ 94.2%) and increased again after the booster dose (100%, 100%, ≥ 99%). Exploratory analyses indicated that rSBA-MenC geometric mean titers were lower and anti-PRP geometric mean concentrations were higher in the infants vaccinated with Hib-MenC-TT compared with the control vaccines at all time points. The safety profiles of the coadministered vaccines were similar in both groups. Conclusions: The Hib-MenC-TT and DTPa-HBV-IPV vaccines are immunogenic with a clinically acceptable safety profile when coadministered as 2 primary doses during infancy and 1 booster dose at 11 months of age.
 
Echovirus 11 is responsible for approximately 70% of neonatal echovirus infection causing significant morbidity and mortality. Although the exact mechanisms of perinatal enterovirus transmission remain to be elucidated, most cases of neonatal echovirus infection are presumed to be acquired from infected cervical secretions intrapartum or from infected mothers postpartum. Two infants with persistent pulmonary hypertension and pneumonia as the primary manifestations of perinatal echovirus 11 infection are reported here.
 
We report a case of human echovirus 11 infection in a neonate at the time of Bornholm disease in late pregnancy of the mother. Mother and baby were found to be infected with the same virus, with a combination of diagnostic virologic techniques, demonstrating likely transmission from mother to baby around the time of delivery.
 
We report an 11-year-old girl with a 3-month history of extended cutaneous leishmaniasis caused by Leishmania major. Oral fluconazole treatment resulted in complete resolution. This result suggests that oral fluconazole might be an alternative to pentavalent antimony in cutaneous lesions of L. major.
 
Long-term persistence of antibodies against hepatitis A and B (anti-HAV and anti-HBs) were evaluated in 1- to 11-year-old children following 2 doses (0, 6 months) of hepatitis A and B vaccine. Ten years postvaccination, all subjects were anti-HAV seropositive (≥15 mIU/mL), 81.7% had anti-HBs antibody concentrations ≥10 mIU/mL. All subjects with anti-HBs concentrations <10 mIU/mL, mounted a vigorous anamnestic response to an HBV vaccine challenge dose indicating the presence of immunologic memory against hepatitis B.
 
Administration of a quadrivalent HPV-6/ 1/16/18 vaccine to 16- to 26-year-old women was highly effective in preventing HPV-6/ 1/16/18-related cervical/vulvar/vaginal precancerous lesions and genital warts. As the risk of acquiring HPV significantly rises after sexual debut, HPV vaccines should have the greatest benefit in sexually naive adolescents. We evaluated the tolerability and immunogenicity of quadrivalent vaccine in males and females 9 to 15 years of age through 18 months postenrollment. In this randomized, double-blind trial, 1781 sexually naive children were assigned (2:1) to quadrivalent HPV-6/11/16/18 vaccine or saline placebo administered at day 1 and months 2 and 6. Serum neutralizing anti-HPV-6/11/16/18 responses were summarized as geometric mean titers (GMTs) and seroconversion rates. Primary analyses were done per-protocol (subjects received 3 doses, had no major protocol violations and were HPV type-specific seronegative at day 1). Adverse experiences were collected by diary card. At month 7, seroconversion rates were > or =99.5% for the 4 vaccine-HPV-types. GMTs and seroconversion rates in boys were noninferior to those in girls (P < 0.001). At month 18, > or =91.5% of vaccine recipients were seropositive, regardless of gender. A higher proportion of vaccine recipients (75.3%) than placebo recipients (50.0%) reported one or more injection-site adverse experiences following any vaccination. Rates of fever were similar between vaccination groups. No serious vaccine-related adverse experiences were reported. In 9- to 15-year-old adolescents, the quadrivalent vaccine was generally well tolerated and induced persistent anti-HPV serologic responses in the majority of subjects for at least 12 months following completion of a three-dose regimen. The vaccine durability supports universal HPV vaccination programs in adolescents to reduce the burden of clinical HPV disease, particularly cervical cancer and precancers.
 
A nine-valent human papillomavirus (9vHPV) vaccine has recently been reported to be safe and highly efficacious against infection and disease related to HPV6/11/16/18/31/33/45/52/58. We evaluated the immunogenicity and safety of the 9vHPV vaccine administered concomitantly with REPEVAX (diphtheria, tetanus, acellular pertussis, and inactivated poliomyelitis vaccine). This open-label, randomized, multicenter study enrolled 1054 males and females ages 11-15 years. Subjects were randomly assigned to each group in a 1:1 ratio. Subjects received a 0.5mL dose of 9vHPV vaccine intramuscularly at day 1, months 2 and 6, and a 0.5 mL dose of REPEVAX either on day 1 (concomitant vaccination group; n = 526) or at month 1 (non-concomitant vaccination group, n = 528). Serologic responses for each vaccine component were tested by one-sided tests of non-inferiority between groups. Systemic and injection-site adverse experiences (AEs) and serious AEs were monitored. Non-inferiority of anti-HPV GMTs and seroconversion rates for all 9vHPV antigens were demonstrated for the concomitant group compared with the non-concomitant group. Seroconversion rates for the 9vHPV vaccine types were ≥99.8% in both groups at month 7. For REPEVAX, noninferiority of immune response was established for diphtheria, tetanus, and all polio and pertussis antigens for both groups. There were no vaccine-related serious AEs. Overall, concomitant administration of 9vHPV vaccine and REPEVAX was generally well tolerated and did not interfere with the immune response to either vaccine. This strategy would minimize the number of visits required to deliver each vaccine individually.NCT01073293.
 
Gallbladder disease in children is an uncommon cause of abdominal pain. Gibson1 in 1734 has provided us with the earliest recorded case of cholecystitis in a child whereupon he removed "three Scotch pints of water of a greenish hue" via aspiration of a distended gallbladder in a 13-year-old who subsequently died. As quoted by Thomas,2 as early as 1829 Lewis recognized the possibility of cholecystitis complicating typhoid fever remarking that "changes in the bile and gallbladder are much more frequent in the course of typhoid fever than in any other acute disease." According to Arnspiger et al.,3 in 1835 Husson described the first pediatric patient with acute acalculous cholecystitis associated with typhoid. Most of the reports in the literature have concerned the adult population and in this regard Da Costa4 in 1898 stated "from the frequency, it might be said constancy, with which infection of the gallbladder happens in typhoid fever, it would be supposed that symptoms referable to it are very common. But it is just the reverse." The largest collection in the literature is that by Thomas2 in 1907 who reported 154 patients with typhoidal cholecystitis of whom 5 were younger than 10 years old and 33 were between 11 and 33 years. A comprehensive review of gallbladder disease in young subjects under 15 years was retrospectively prepared by Potter5 in 1928. Twenty-five of 226 (11%) cases resulted from acute typhoidal cholecystitis. Since that era acute cholecystitis resulting from typhoid has become a rare disease. Rubenstein6 in 1943 presented 4 patients all older than 25 years of age and Glenn and Hill7 in their 20-year study in 1951 specified a single 9-year-old patient who succumbed to the illness. The incidence of this as an acute complication of typhoid has been noted to be between 0.5 and 2% in all age groups8,9; the precise estimation of this event in children is not known. Presented herein is an 11-year-old girl who recovered from acute acalculous typhoid cholecystitis following medical therapy. (C) Williams & Wilkins 1988. All Rights Reserved.
 
Corticosteroid treatment for meningococcal disease is debated. We report a high risk of death (OR 4.68, 95% CI [1.91; 11.46]; p=0.001) without corticosteroid treatment when meningococcal disease is provoked by isolates belonging to the hyper-invasive genotype ST-11. Genotypes of meningococcal isolates should be considered with corticosteroids therapy for meningococcal disease.
 
Among a group of hospitalized children in Fukuoka, southern Japan, an epidemic of pharyngoconjunctival fever-like disease caused by adenovirus type 11 was observed in the autumn of 1988. Of the 47 children studied 38 were seronegative in neutralizing antibody for adenovirus type 11 before the epidemic, and seroconversion occurred in 16 (42%) including 5 subclinical cases. Of the 11 symptomatic patients the incidences of conjunctivitis, pharyngitis and fever were 91, 64 and 46%, respectively. Four patients (36%) had all three symptoms. Fifteen patients (94%) were boys. The sex predominance and high incidence of conjunctivitis suggested that infection may have been transmitted in the large bathroom where boys took baths together.
 
Healthy and at risk children are susceptible to the morbidity and mortality associated with viral-induced respiratory diseases, including respiratory syncytial virus (RSV) and influenza. The World Health Organization is attempting to develop and distribute effective vaccines to prevent/reduce key viral respiratory diseases. The goals of a vaccination program for viral respiratory infections include the prevention of lower respiratory tract infections and prevention of infection-associated morbidities, hospitalization and mortality. This article explores influenza and RSV vaccine developments. There are 2 influenza vaccines, trivalent inactivated and live, cold-adapted, attenuated. Trivalent inactivated vaccine is indicated for persons older than 6 months of age. Currently <10%, <30% and <30% of healthy children, healthy adults and high risk children, respectively, are vaccinated. Efficacy is from 70 to 90% in healthy adults younger than 65 years of age and 30-90% in children, with lower efficacy in younger children. Live, cold-adapted, attenuated vaccine is indicated for healthy persons 5-49 years of age and usually is 70-90% effective. Various RSV vaccine formulations are being investigated. The Advisory Committee on Immunization Practices (ACIP) recommends influenza vaccination for children 6-23 months old. Studies support immunization of all children, not only those at high risk. Current ACIP recommendations focus on high risk persons and do not include school age children. A universal immunization program for all children could benefit the entire community. Effective vaccines are available for some viral respiratory pathogens (eg, influenza virus), but not for most mucosally restricted respiratory viral pathogens. Research should continue into safe and effective vaccines for all childhood viral illnesses.
 
Pneumococcus is a leading cause of childhood pneumonia worldwide. Pneumococcal conjugate vaccines (PCV) have demonstrated efficacy against childhood invasive pneumococcal disease (IPD) and pneumonia in the United States and Africa. No information is available from Asia on the impact of PCV on childhood pneumonia. We conducted a randomized, placebo-controlled, double-blind trial in Bohol, the Philippines (ISRCTN 62323832). Children 6 weeks to <6 months of age were randomly allocated to receive 3 doses of either an 11-valent PCV (11PCV, sanofi pasteur, Lyon, France) or a saline placebo, with a minimum interval of 4 weeks between doses to determine vaccine efficacy (VE) against the primary outcome of a child experiencing first episode of community-acquired radiologically defined pneumonia in the first 2 years of life. Secondary end points were clinical pneumonia, IPD, safety, and immunogenicity. Twelve thousand one hundred ninety-one children were enrolled. By per protocol (PP) analysis, 93 of 6013 fully vaccinated 11PCV recipient children had a first episode of radiologic pneumonia compared with 120 of 6018 placebo recipients. VE against radiologically defined pneumonia for the PP cohort of children 3 to 23 months old was 22.9% (95% CI: -1.1, 41.2; P = 0.06), for the prespecified subgroups of children 3 to 11 months of age, 34.0% (95% CI: 4.8, 54.3; P = 0.02), and of those 12 to 23 months old, 2.7% (95% CI: -43.5, 34.0; P = 0.88). By intent-to-treat (ITT) analysis, 119 of 6097 11PCV recipient children had an episode of radiologic pneumonia compared with 141 of 6094 placebo recipients. VE against radiologic pneumonia for the ITT cohort of children <2 years old was 16.0% (95% CI -7.3, 34.2; P = 0.16), for a subgroup of children <12 months of age, 19.8% (95% CI: -8.8, 40.8; P = 0.15). VE against clinical pneumonia by PP was not significant (VE 0.1%; 95% CI -9.4, 8.7; P = 0.99). IPD was rare: only 3 cases of IPD due to vaccine serotypes were observed during the study. 11PCV was immunogenic and well tolerated. Among 11PCV recipients, a small excess of serious adverse respiratory events was observed in the first 28 days after the first and second dose of vaccine, and of nonrespiratory events after the first dose. An excess of pneumonia episodes in 11PCV recipients in the month following the second dose of vaccination was the principal reason for lower VE by ITT analysis than by PP analysis. In PP analysis, a 22.9% reduction of community-acquired radiologically confirmed pneumonia in children younger than 2 years of age in the 11-valent tetanus-diphtheria toxoid-conjugated PCV vaccinated group was observed; a reduction similar as observed in other PCV trials. We could not demonstrate any VE against clinical pneumonia. Our finding confirms for the first time that in a low-income, low-mortality developing country in Asia, at least one-fifth of radiologically confirmed pneumonia is caused by pneumococcus, and thus preventable by PCV. Whether PCV should be included in national program in such settings, however, depends on careful country specific disease burden measurement and cost-effectiveness calculation.
 
Little is known about the risk of tuberculosis transmission from children. We reviewed the published literature on the transmission of tuberculosis during outbreaks involving children 3 to 11 years of age and report that transmission rates among close contacts in school outbreaks are on average higher (weighted average 69.8% vs. 39.3%) if the index case is a child than an adult.
 
Between July 18 and August 5, 1986, a cluster of echovirus 11 infections occurred in hospitalized neonates. Ten infants were affected and one died. All cases occurring after the index case were infants who were in the nursery for at least 1 day when the index patient was also present. Risk factors for secondary infection included low birth weight or gestational age and receipt of antibiotics, red blood cell transfusions, nasogastric intubation or gavage feedings. Because viral infection had not been suspected in the index patient, isolation measures were not instituted until after onset of secondary cases. We conclude that more severely ill infants receiving intensive levels of care are at increased risk for nosocomial enteroviral infection. These infants may have a greater likelihood of exposure to the virus and/or increased host susceptibility. Outbreaks caused by cross-infection may be preventable by early recognition of patients colonized or infected with potentially pathogenic agents and prompt institution of appropriate isolation measures.
 
Candida species is an important cause of nosocomial infection in neonatal intensive care units (NICUs). However, most reports in China have been limited to single institutions. The aim of this study is to investigate the epidemiology of invasive candidiasis in multiple NICUs across China. We retrospectively collected demographic data, clinical characteristics, microbiological results and outcome of preterm infants with invasive candidiasis discharged from 11 academic tertiary NICUs during January 2009 - December 2011. There were 30,045 preterm infants discharged from 11 NICUs during the study period. We detected 223 infants with invasive candidiasis, resulting in an incidence of 0.74 cases per 100 preterm discharges from NICUs. In very low birth weight infants, the incidence was 3.42 cases per 100 VLBW discharges. Mean gestational age of infected infants was 31.4 weeks and median birth weight 1410 gram. Among the cohort of infants with invasive candidiasis, 214 (96.0%) infants had positive blood culture for fungus, 5 infants had positive urine culture, 3 from cerebrospinal fluid (CSF) and 1 from articular effusion in the shoulder joint. Among the cohort of infants with candidemia, 48 (22.4%) infants had fungal meningitis. Candida albicans accounted for 57.4% of total positive cultures. Overall mortality attributable to invasive candidiasis was 19.3%. Invasive candidiasis is a common problem among preterm neonates in China, especially among VLBW infants and it is associated with a high mortality. The preponderance of infections was due to Candida albicans.
 
We report here a neonate with echovirus 11 hepatitis, pneumonitis, meningitis, disseminated intravascular coagulation, decreased renal function and anemia, who survived after receiving a large dose of IVIG and supportive care. Echovirus 11 antibody was absent pretreatment but present in a posttreatment serum specimen and in the IVIG preparation used.
 
A 6-year multicenter therapeutic study was performed on 1100 children with brucellosis in order to compare several antibiotic combinations and duration of treatment. The patients were randomized to receive oral therapy with oxytetracycline, doxycycline, rifampin and trimethoprim-sulfamethoxazole (TMP/SMX) either alone or in combination with each other or combined with streptomycin or gentamicin injections. The patients were also randomized into three groups based on the duration of oral therapy: 500 patients were treated for 3 weeks; 350 for 5 weeks; and 250 for 8 weeks. When intramuscular aminoglycosides were used, streptomycin was given for 2 weeks and gentamicin for 5 days. In oral monotherapy oxytetracycline, doxycycline and rifampin showed comparable results with low relapse rates (less than or equal to 9%) and no statistically significant differences were found among 3-, 5- or 8-week durations of therapy. TMP/SMX alone showed an unacceptably high relapse rate (30%) with all durations of therapy. In combined oral therapy rifampin plus oxytetracycline, rifampin plus TMP/SMX and oxytetracycline plus TMP/SMX showed comparable results with low relapse rates ranging from 4 to 8% in patients receiving therapy for 3 or 5 weeks, no relapses occurred in patients treated for 8 weeks. When oral monotherapy was combined with either streptomycin or gentamicin, very few relapses were seen, irrespective of the duration of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
 
We cultured middle ear fluid specimens obtained by tympanocentesis from 111 Colombian infants and children, ages 11 days to 11 years, with acute otitis media. Bacteria were isolated in 82 patients (74%). Haemophilus influenzae, the most common isolate, was present in 40 cases (36%); 32 were nontypable strains and 8 were type b. Streptococcus pneumoniae, identified in 26 cases (22%), was the second most common pathogen. All H. influenzae and S. pneumoniae strains were susceptible to ampicillin and penicillin, respectively. We conclude that amoxicillin remains the drug of choice for treatment of acute otitis media in our country.
 
To determine changes in the incidence of candidemia in a neonatal intensive care unit (NICU) during a 15-year period (1981 to 1995) and to compare the prevalence and case fatality rates of Candida albicans and Candida parapsilosis infections. A retrospective study was conducted of candidemia occurring in infants in a NICU between January 1, 1981, and December 31, 1995. Cases were identified through computerized searching of a microbiology blood culture database. Candidemia was considered contributory to mortality if death occurred within 3 days of positive blood cultures or if there was autopsy evidence of disseminated candidiasis. One hundred eleven cases of candidemia occurred in 107 infants, representing 1% of all NICU patients during the study period. The rate of candidemia in the NICU increased from 2.5 cases per 1000 admissions in 1981 to 1985, to 4.6 per 1000 admissions in 1986 to 1990 and to 28.5 per 1000 in 1991 to 1995 (P = 0.001). C. albicans was the predominant cause of candidemia between 1981 and 1990. C. parapsilosis was the most prevalent species between 1991 and 1995, causing 53 of 89 cases (60%). The mortality from C. albicans, 13 of 50 cases (26%), was significantly higher than the mortality from C. parapsilosis, 2 of 54 (4%) (P = 0.002; relative risk, 7; 95% confidence interval, 1.7 to 30). The rate of candidemia in our neonatal intensive care unit increased >11-fold in the 15 years from 1981 to 1995; the prevalent Candida species shifted from C. albicans to C. parapsilosis; and candidemia associated with C. albicans has significantly higher mortality than with C. parapsilosis.
 
Treatment of childhood brucellosis is controversial and is currently dependent on inclusion of aminoglycoside antibiotics which are both costly and potentially toxic. Hence an alternate mode of therapy preferably dependent exclusively on oral agents is desirable because this decreases medical cost. In this study we prospectively treated 113 children with a combination of two oral agents, trimethoprim-sulfamethoxazole (10 to 12 mg/kg trimethoprim, 50 to 60 mg/kg sulfamethoxazole and rifampin 15 to 20 mg/kg in two divided doses for 6 weeks. The treatment was well-tolerated and all patients responded by defervescence of fever and resolution of all symptoms within 1 to 3 weeks. Relapse after 6 months occurred in four children all of whom responded to repeat therapy by the same agents. We conclude that the combination of trimethoprim-sulfamethoxazole and rifampin is both cost-effective and safe for the treatment of childhood brucellosis.
 
The aim of this study was to determine the causes of fever of unknown origin, to evaluate new diagnostic tests and to elucidate risk factors for chronic or life-threatening disorders. The medical records of 113 children who had undiagnosed fever for at least 3 weeks were reviewed. Infection (N = 41) was the most frequent cause of fever of unknown origin. Respiratory tract infections were the most common causes in infants and endocarditis and tuberculosis were more frequent in older children. Neoplastic disorders (N = 11) occurred in children older than one year. Juvenile rheumatoid arthritis (N = 9) was the most common collagen-vascular disorder (N = 15). Miscellaneous disorders and factitious fever occurred in 21 and 4 cases, respectively. Twenty-two patients remained undiagnosed. History and physical examination led to a final diagnosis in 81% of cases. Abdominal ultrasonography was performed in 71 patients (61%) and was helpful for diagnosis in 15%. Children with life-threatening or chronic disorders (N = 58) were older than those with self-limiting conditions (N = 55; P = 0.017). Cardiovascular and articular signs and symptoms were more frequent in the former group (P = 0.01).
 
The development of vaccines against pandemic influenza viruses for use in children is a public health priority. In this phase II, randomized, open study, the immunogenicity and reactogenicity of H5N1 A/Vietnam/1194/2004 (NIBRG-14) (clade 1) prepandemic influenza vaccine were assessed in children aged 3 to 5 and 6 to 9 years. Children were randomized to receive 2 doses, given 21 days apart, of A/Vietnam/1194/2004 vaccine containing 1.9 microg or 3.75 microg hemagglutinin antigen (HA), adjuvanted with a tocopherol-based oil-in-water emulsion (AS03) containing 11.86 mg (AS03(A)) or 5.93 mg (AS03(B)) tocopherol. Control groups received 2 doses of trivalent influenza vaccine (TIV). Humoral immune responses, reactogenicity, and safety were the primary outcome measures; cross-reactivity and cell-mediated responses were also assessed (NCT00502593). Between 49 and 51 children in each age stratum (aged 3-5 and 6-9 years) received H5N1 vaccine, and between 17 and 18 children in each age stratum received TIV. After the second dose, recipients of H5N1 vaccine (1.9 microg HA/AS03(B), 3.75 microg HA/AS03(B), and 3.75 microg HA/AS03(A)) achieved humoral antibody titers against the vaccine-homologous strain, which fulfilled the United States influenza vaccines licensure criteria for immunogenicity. With the exception of 1 child, there were no H5N1 immune responses in children who received TIV. The most frequent injection-site event was pain in all groups, and the H5N1 vaccine had a clinically acceptable reactogenicity and safety profile. Exploratory analyses in children aged 3 to 5 years indicated that the induction of CD4 T-cell responses polarized in favor of a T-helper 1 profile. The results showed that 2 doses of AS03-adjuvanted H5N1 influenza vaccine at antigen-sparing doses of 1.9 microg or 3.75 microg HA elicited broad and persistent immune responses with acceptable reactogenicity, and without safety concerns, in children aged 3 to 9 years.
 
is a common cause of respiratory disease, but little is known about asymptomatic infection, duration of persistent respiratory tract infection and seasonal changes of prevalence in a normal large sample size pediatric population. We studied the prevalence of infection in 1211 children of 3 age groups: 3- to 4-year-old kindergarten children ( = 184) and schoolchildren attending first and second ( = 353) or seventh and eighth grade classes ( = 674). Polymerase chain reaction and enzyme immunoassay detection (PCR-EIA) of throat swabs were used. Respiratory tract symptoms (cough, rhinitis, earache or sore throat) were recorded in 1028 schoolchildren. Follow-up examinations in PCR-positive patients were performed until negative. PCR was positive in 68 children (5.6%) without significant age and gender related differences in prevalence. Epidemics were confirmed with a prevalence up to 24% in a primary school in December and April. In schoolchildren, asymptomatic infection was a common feature, reaching 54% (32 of 59) of PCR-EIA positives. The rate of asymptomatic infection was 6% (32 of 531 schoolchildren without symptoms). Of the 32 asymptomatic PCR-EIA positives, 26 (81%) were children attending seventh and eighth grade classes. In 3 children PCR-EIA remained positive at 3 to 5 weeks and became negative during the next 7 to 9 weeks. One of 2 schoolchildren with persistent infection was asymptomatic. We conclude that infection is common in the childhood population studied with seasonal variations in prevalence and epidemic-like occurrence. Asymptomatic infection occurs, especially in teenagers, but persistent infection is rare.
 
Top-cited authors
Manish Patel
  • Junagadh Agricultural University
David Goldblatt
  • University of London
Nigel Curtis
  • The Royal Children's Hospital
Janet R Casey
  • University of Rochester
Monica M Farley
  • Emory University