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Pediatrics (Journal of American Academy of Pediatrics) January 2007 | Volume 119 | Issue(pp.1-227)(1 ARTICLES Accuracy and Interpretation of Rapid Influenza Tests in Children Carlos G. Grijalva, Katherine A. Poehling, Kathryn M. Edwards, Geoffrey A. Weinberg, Mary A. Staat, Marika K. Iwane, William Schaffner, and Marie R. Griffin Pediatrics 2007; 119: e6-e11. Cost-Effectiveness of Routine Childhood Vaccination for Hepatitis A in the United States David B. Rein, Katherine A. Hicks, Kathleen E. Wirth, Kaafee Billah, Lyn Finelli, Anthony E. Fiore, Thomas J. Hoerger, Beth P. Bell, and Gregory L. Armstrong Pediatrics 2007; 119: e12-e21. The Economics of Routine Childhood Hepatitis A Immunization in the United States: The Impact of Herd Immunity Gregory L. Armstrong, Kaafee Billah, David B. Rein, Katherine A. Hicks, Kathleen E. Wirth, and Beth P. Bell Pediatrics 2007; 119: e22-e29. Is Dieting Advice From Magazines Helpful or Harmful? Five-Year Associations With Weight- Control Behaviors and Psychological Outcomes in Adolescents Patricia van den Berg, Dianne Neumark-Sztainer, Peter J. Hannan, and Jess Haines Pediatrics 2007; 119: e30-e37. Childhood Mental Ability in Relation to Food Intake and Physical Activity in Adulthood: The 1970 British Cohort Study G. David Batty, Ian J. Deary, Ingrid Schoon, and Catharine R. Gale Pediatrics 2007; 119: e38-e45. The Status of Academic General Pediatrics: No Longer Endangered? Tina L. Cheng, Diane Markakis, and Thomas G. DeWitt Pediatrics 2007; 119: e46-e52. The Use of the World Wide Web by Medical Journals in 2003 and 2005: An Observational Study David L. Schriger, Sripha Ouk, and Douglas G. Altman Pediatrics 2007; 119: e53-e60. Infection in the First 2 Years of Life and Autism Spectrum Disorders Nila J. Rosen, Cathleen K. Yoshida, and Lisa A. Croen Pediatrics 2007; 119: e61-e69. To What Extent Do Pediatricians Accept Computer-Based Dosing Suggestions? Brigid K. Killelea, Rainu Kaushal, Mary Cooper, and Gilad J. Kuperman Pediatrics 2007; 119: e69-e75. Clinical Disease in Children Associated With Newly Described Coronavirus Subtypes Jane Kuypers, Emily T. Martin, Judson Heugel, Nancy Wright, Rhoda Morrow, and Janet A. Englund Pediatrics 2007; 119: e70-e76. Prevention of Pediatric Medication Errors by Hospital Pharmacists and the Potential Benefit of Computerized Physician Order Entry Jerome K. Wang, Nicole S. Herzog, Rainu Kaushal, Christine Park, Carol Mochizuki, and Scott R. Weingarten Pediatrics 2007; 119: e77-e85. Caregiver Health Literacy and the Use of Child Health Services Lee M. Sanders, Valerie T. Thompson, and James D. Wilkinson Pediatrics 2007; 119: e86-e92. At What Age Can Children Report Dependably on Their Asthma Health Status? Lynn M. Olson, Linda Radecki, Mary Pat Frintner, Kevin B. Weiss, Jon Korfmacher, and Robert M. Siegel Pediatrics 2007; 119: e93-e102. A National Assessment of Knowledge, Attitudes, and Confidence of Prehospital Providers in the Assessment and Management of Child Maltreatment David Markenson, Michael Tunik, Arthur Cooper, Lenora Olson, Lawrence Cook, Hedda Matza-Haughton, Marsha Treiber, William Brown, Phil Dickinson, and George Foltin Pediatrics 2007; 119: e103-e108. The Effects of Oxandrolone and Exercise on Muscle Mass and Function in Children With Severe Burns Rene Przkora, David N. Herndon, and Oscar E. Suman Pediatrics 2007; 119: e109-e116. Pediatrician Characteristics Associated With Attention to Spirituality and Religion in Clinical Practice Daniel H. Grossoehme, Judith R. Ragsdale, Christine L. McHenry, Celia Thurston, Thomas DeWitt, and Larry VandeCreek Pediatrics 2007; 119: e117-e123. Lactobacillus reuteri (American Type Culture Collection Strain 55730) Versus Simethicone in the Treatment of Infantile Colic: A Prospective Randomized Study Francesco Savino, Emanuela Pelle, Elisabetta Palumeri, Roberto Oggero, and Roberto Miniero Pediatrics 2007; 119: e124-e130. Improvement in Booster Seat Use in Tennessee Veronica L. Gunn, Rhonda M. Phillippi, and William O. Cooper Pediatrics 2007; 119: e131-e136. Breastfeeding and Infant Eczema in the First Year of Life in the KOALA Birth Cohort Study: A Risk Period–Specific Analysis Bianca E. P. Snijders, Carel Thijs, Ischa Kummeling, John Penders, and Piet A. van den Brandt Pediatrics 2007; 119: e137-e141. Physician Advice About Being Overweight: Association With Self-Reported Weight Loss, Dietary, and Physical Activity Behaviors of US Adolescents in the National Health and Nutrition Examination Survey, 1999–2002 Ashima K. Kant and Patricia Miner Pediatrics 2007; 119: e142-e147. Identification of Overweight Status Is Associated With Higher Rates of Screening for Comorbidities of Overweight in Pediatric Primary Care Practice Kimberley J. Dilley, Lisa A. Martin, Christine Sullivan, Roopa Seshadri, Helen J. Binns for the Pediatric Practice Research Group Pediatrics 2007; 119: e148-e155. Revalidation of the Score for Neonatal Acute Physiology in the Vermont Oxford Network John A. F. Zupancic, Douglas K. Richardson, Jeffrey D. Horbar, Joseph H. Carpenter, Shoo K. Lee, Gabriel J. Escobar, and Vermont Oxford Network SNAP Pilot Project Participants Pediatrics 2007; 119: e156-e163. Prevention of Necrotizing Enterocolitis in Preterm Infants: A 20-Year Experience Jeff Pietz, Babu Achanti, Lawrence Lilien, Erin Clifford Stepka, and Sudhir Ken Mehta Pediatrics 2007; 119: e164-e170. Cord Blood Cytokines and Acute Lower Respiratory Illnesses in the First Year of Life Ngoc P. Ly, Sheryl L. Rifas-Shiman, Augusto A. Litonjua, Arthur O. Tzianabos, Bianca Schaub, Begoña Ruiz- Pérez, Kelan G. Tantisira, Patricia W. Finn, Matthew W. Gillman, Scott T. Weiss, and Diane R. Gold Pediatrics 2007; 119: e171-e178. Antipolyribosyl Ribitol Phosphate Response of Premature Infants to Primary and Booster Vaccination With a Combined Diphtheria-Tetanus-Acellular Pertussis-Hepatitis B- Inactivated Polio Virus/Haemophilus influenzae Type b Vaccine Felix Omeñaca, José Garcia-Sicilia, Pilar García-Corbeira, Reyes Boceta, and Victorio Torres Pediatrics 2007; 119: e179-e185. Hopeful Thinking and Level of Comfort Regarding Providing Pediatric Palliative Care: A Survey of Hospital Nurses Chris Feudtner, Gina Santucci, James A. Feinstein, C. Rick Snyder, Mary T. Rourke, and Tammy I. Kang Pediatrics 2007; 119: e186-e192. Use of Serologic Markers as a Screening Tool in Inflammatory Bowel Disease Compared With Elevated Erythrocyte Sedimentation Rate and Anemia Nasim Sabery and Dorsey Bass Pediatrics 2007; 119: e193-e199. Sleep Arrangements and Behavior of Bed-Sharing Families in the Home Setting Sally A. Baddock, Barbara C. Galland, Barry J. Taylor, and David P.G. Bolton Pediatrics 2007; 119: e200-e207. Barriers to the Identification and Management of Psychosocial Issues in Children and Maternal Depression Sarah McCue Horwitz, Kelly J. Kelleher, Ruth E.K. Stein, Amy Storfer-Isser, Eric A. Youngstrom, Elyse R. Park, Amy M. Heneghan, Peter S. Jensen, Karen G. O'Connor, and Kimberly Eaton Hoagwood Pediatrics 2007; 119: e208-e218. Potential for Donation After Cardiac Death in a Children's Hospital Amy L. Durall, Peter C. Laussen, and Adrienne G. Randolph Pediatrics 2007; 119: e219-e224. Early Life Exposure to Antibiotics and the Subsequent Development of Eczema, Wheeze, and Allergic Sensitization in the First 2 Years of Life: The KOALA Birth Cohort Study Ischa Kummeling, Foekje F. Stelma, Pieter C. Dagnelie, Bianca E. P. Snijders, John Penders, Machteld Huber, Ronald van Ree, Piet A. van den Brandt, and Carel Thijs Pediatrics 2007; 119: e225-e231. XXY (Klinefelter Syndrome): A Pediatric Quantitative Brain Magnetic Resonance Imaging Case-Control Study Jay N. Giedd, Liv S. Clasen, Gregory L. Wallace, Rhoshel K. Lenroot, Jason P. Lerch, Elizabeth Molloy Wells, Jonathan D. Blumenthal, Jean E. Nelson, Julia W. Tossell, Catherine Stayer, Alan C. Evans, and Carole A. Samango-Sprouse Pediatrics 2007; 119: e232-e240. Pulmonary Endostatin Perinatally and in Lung Injury of the Newborn Infant Joakim Janér, Sture Andersson, Caj Haglund, and Patrik Lassus Pediatrics 2007; 119: e241-e246. SunSafe in the Middle School Years: A Community-wide Intervention to Change Early- Adolescent Sun Protection Ardis L. Olson, Cecelia Gaffney, Pamela Starr, Jennifer J. Gibson, Bernard F. Cole, and Allen J. Dietrich Pediatrics 2007; 119: e247-e256. The Effect of Birth in Secondary- or Tertiary-Level Hospitals in Finland on Mortality in Very Preterm Infants: A Birth-Register Study Liisi Rautava, Liisa Lehtonen, Mikko Peltola, Emmi Korvenranta, Heikki Korvenranta, Miika Linna, Mikko Hallman, Sture Andersson, Mika Gissler, Jaana Leipälä, Outi Tammela, Unto Häkkinen for the PERFECT Preterm Infant Study Group Pediatrics 2007; 119: e257-e263. The Role of CYP2A6 in the Emergence of Nicotine Dependence in Adolescents Janet Audrain-McGovern, Nael Al Koudsi, Daniel Rodriguez, E. Paul Wileyto, Peter G. Shields, and Rachel F. Tyndale Pediatrics 2007; 119: e264-e274. A Randomized, Controlled Trial of Heparin Versus Placebo Infusion to Prolong the Usability of Peripherally Placed Percutaneous Central Venous Catheters (PCVCs) in Neonates: The HIP (Heparin Infusion for PCVC) Study Prakesh S. Shah, Angela Kalyn, Prakash Satodia, Michael S. Dunn, Boriana Parvez, Alan Daneman, Shia Salem, Phyllis Glanc, Arne Ohlsson, and Vibhuti Shah Pediatrics 2007; 119: e284-e291. Will Pediatricians Adopt the New Rotavirus Vaccine? Allison Kempe, Matthew F. Daley, Umesh D. Parashar, Lori A. Crane, Brenda L. Beaty, Shannon Stokley, Jennifer Barrow, Christine Babbel, L. Miriam Dickinson, Marc-Alain Widdowson, James P. Alexander, and Stephen Berman Pediatrics 2007; 119: 1-10. Efficacy, Immunogenicity, and Safety of a Pentavalent Human-Bovine (WC3) Reassortant Rotavirus Vaccine at the End of Shelf Life Stan L. Block, Timo Vesikari, Michelle G. Goveia, Stephen B. Rivers, Ben A. Adeyi, Michael J. Dallas, Jeffrey Bauder, John W. Boslego, Penny M. Heaton for the Pentavalent Rotavirus Vaccine Dose Confirmation Efficacy Study Group Pediatrics 2007; 119: 11-18. Cystic Fibrosis Diagnosed After 2 Months of Age Leads to Worse Outcomes and Requires More Therapy Erika J. Sims, Allan Clark, Jonathan McCormick, Gita Mehta, Gary Connett, Anil Mehta on behalf of the United Kingdom Cystic Fibrosis Database Steering Committee Pediatrics 2007; 119: 19-28. No Improvement in Outcome of Nationwide Extremely Low Birth Weight Infant Populations Between 1996–1997 and 1999–2000 Viena Tommiska, Kirsti Heinonen, Liisa Lehtonen, Martin Renlund, Timo Saarela, Outi Tammela, Martti Virtanen, and Vineta Fellman Pediatrics 2007; 119: 29-36. Improved Neurodevelopmental Outcomes for Extremely Low Birth Weight Infants in 2000– 2002 Deanne Wilson-Costello, Harriet Friedman, Nori Minich, Bonnie Siner, Gerry Taylor, Mark Schluchter, and Maureen Hack Pediatrics 2007; 119: 37-45. Is a "Wage-Payment" Model for Research Participation Appropriate for Children? Stephen J. Bagley, William W. Reynolds, and Robert M. Nelson Pediatrics 2007; 119: 46-51. Effects of Selective Serotonin Reuptake Inhibitors and Venlafaxine During Pregnancy in Term and Preterm Neonates Ema Ferreira, Ana Maria Carceller, Claire Agogué, Brigitte Zoé Martin, Martin St-André, Diane Francoeur, and Anick Bérard Pediatrics 2007; 119: 52-59. Low-Income Uninsured Children With Special Health Care Needs: Why Aren't They Enrolled in Public Health Insurance Programs? Jennifer Haley and Genevieve Kenney Pediatrics 2007; 119: 60-68. Binge Drinking and Associated Health Risk Behaviors Among High School Students Jacqueline W. Miller, Timothy S. Naimi, Robert D. Brewer, and Sherry Everett Jones Pediatrics 2007; 119: 76-85. Adverse Associations of Sleep Problems in Australian Preschoolers: National Population Study Harriet Hiscock, Louise Canterford, Obioha C. Ukoumunne, and Melissa Wake Pediatrics 2007; 119: 86-93. Pediatric Hospital and Intensive Care Unit Capacity in Regional Disasters: Expanding Capacity by Altering Standards of Care Robert K. Kanter and John R. Moran Pediatrics 2007; 119: 94-100. Adolescent Depression Screening in Primary Care: Feasibility and Acceptability Rachel A. Zuckerbrot, Laura Maxon, Dana Pagar, Mark Davies, Prudence W. Fisher, and David Shaffer Pediatrics 2007; 119: 101-108. EXPERIENCE & REASON T-Cell–Based Diagnosis of Neonatal Multidrug-Resistant Latent Tuberculosis Infection Luca Richeldi, Katie Ewer, Monica Losi, Barbara M. Bergamini, Kerry Millington, Leonardo M. Fabbri, and Ajit Lalvani Pediatrics 2007; 119: e1-e5. Mycoplasma pneumoniae, Splenic Infarct, and Transient Antiphospholipid Antibodies: A New Association? Char M. Witmer, Andrew P. Steenhoff, Samir S. Shah, and Leslie J. Raffini Pediatrics 2007; 119: e292-e295. First Report of Autologous Cord Blood Transplantation in the Treatment of a Child With Leukemia Ammar Hayani, Eberhard Lampeter, David Viswanatha, David Morgan, and Sharad N. Salvi Pediatrics 2007; 119: e296-e300. An Unusual Case of Severe Therapy-Resistant Hypertension in a Newborn Stefan G. Kiessling, Nitin Wadhwa, Vesna M. Kriss, Joseph Iocono, and Nirmala S. Desai Pediatrics 2007; 119: e301-e304. STATE-OF-THE-ART REVIEW ARTICLES New Developments in the Treatment of Hypoplastic Left Heart Syndrome Bahaaldin Alsoufi, Jayme Bennetts, Subodh Verma, and Christopher A. Caldarone Pediatrics 2007; 119: 109-117. REVIEW ARTICLES Adverse Events Associated With Pediatric Spinal Manipulation: A Systematic Review Sunita Vohra, Bradley C. Johnston, Kristie Cramer, and Kim Humphreys Pediatrics 2007; 119: e275-e283. Will Esophageal Impedance Replace pH Monitoring? Yvan Vandenplas, Silvia Salvatore, Mario C. Vieira, and Bruno Hauser Pediatrics 2007; 119: 118-122. SPECIAL ARTICLES Legal and Ethical Considerations: Risks and Benefits of Postpartum Depression Screening at Well-Child Visits Linda H. Chaudron, Peter G. Szilagyi, Amy T. Campbell, Kyle O. Mounts, and Thomas K. McInerny Pediatrics 2007; 119: 123-128. COMMENTARIES Identifying Children With Autism Early? Vidya Bhushan Gupta, Susan L. Hyman, Chris Plauché Johnson, James Bryant, Barbara Byers, Ronald Kallen, Susan E. Levy, Scott M. Myers, Alan I. Rosenblatt, and Marshalyn Yeargin-Allsopp Pediatrics 2007; 119: 152-153. Stimulant-Drug Therapy for Attention-Deficit Disorder (With or Without Hyperactivity) and Sudden Cardiac Death Matthew Knight Pediatrics 2007; 119: 154-155. The Meaning of "Early" Diagnosis in a New Era of Cystic Fibrosis Care Philip M. Farrell Pediatrics 2007; 119: 156-157. The Limits of Viability and the Uncertainty of Neuroprotection: Challenges in Optimizing Outcomes in Extreme Prematurity Michael E. Msall Pediatrics 2007; 119: 158-160. FROM THE AMERICAN ACADEMY OF PEDIATRICS Access to Optimal Emergency Care for Children Committee on Pediatric Emergency Medicine Pediatrics 2007; 119: 161-164. Cord Blood Banking for Potential Future Transplantation Section on Hematology/Oncology and Section on Allergy/Immunology Pediatrics 2007; 119: 165-170. Prevention of Rotavirus Disease: Guidelines for Use of Rotavirus Vaccine Committee on Infectious Diseases Pediatrics 2007; 119: 171-182. The Importance of Play in Promoting Healthy Child Development and Maintaining Strong Parent-Child Bonds Kenneth R. Ginsburg, and the Committee on Communications and the Committee on Psychosocial Aspects of Child and Family Health Pediatrics 2007; 119: 182-191. Preventing and Treating Homesickness Christopher A. Thurber, Edward Walton and the Council on School Health Pediatrics 2007; 119: 192-201. Office-Based Counseling for Unintentional Injury Prevention H. Garry Gardner and the Committee on Injury, Violence, and Poison Prevention Pediatrics 2007; 119: 202-206. Recommended Immunization Schedules for Children and Adolescents—United States, 2007 Committee on Infectious Diseases Pediatrics 2007; 119: 207-208. LETTERS TO THE EDITOR Intratracheal Sildenafil in the Newborn With Pulmonary Hypertension Miguel Martell, Fernanda Blasina, Fernando Silvera, Salvador Tellechea, Carolina Godoy, Lucía Vaamonde, Luana Benenatti, and Walter Olivera Pediatrics 2007; 119: 215-216. Intratracheal Sildenafil in the Newborn With Pulmonary Hypertension: In Reply Hernando Baquero and Augusto Sola Pediatrics 2007; 119: 216. The Need to Assess Benefits and Not Just Risks of 100% Oxygen for Newborn Resuscitation Henry J. Rozycki Pediatrics 2007; 119: 217. The Need to Assess Benefits and Not Just Risks of 100% Oxygen for Newborn Resuscitation: In Reply Ola Didrik Saugstad, Siddarth Ramji, and Maximo Vento Pediatrics 2007; 119: 217a-219. Give Synagis via Home Health John Goldenring Pediatrics 2007; 119: 219. Predictive Model for Lyme Meningitis: A Reply Robert A. Avery, Gary Frank, and Stephen C. Eppes Pediatrics 2007; 119: 219a-220. Treated Hypotension in Extremely Low Birth Weight Infants Joseph A. Kitterman and Roderic H. Phibbs Pediatrics 2007; 119: 220-221. The Research Failed, but the Patients Are Doing Well Kathi J. Kemper and Teresa Shaw Pediatrics 2007; 119: 221-222. Trends in Asthma Prevalence and Recommended Number of Childhood Immunizations Are Not Parallel Rachel Enriquez, Victoria Persky, and Tina Hartert Pediatrics 2007; 119: 222-223. The Economic Burden of All-Terrain Vehicle–Related Pediatric Deaths in the United States Jim Helmkamp and Bruce A. Lawrence Pediatrics 2007; 119: 223-225. Further Efforts to Reduce the Incidence of Neural Tube Defects Robert L. Brent and Godfrey P. Oakley, Jr Pediatrics 2007; 119: 225-226. How Much Sucrose Is Too Much Sucrose? C. Celeste Johnston, Francoise Filion, Laurie Snider, Catherine Limperopoulos, Annette Majnemer, Ermelinda Pelausa, Heather Cake, Sharon Stone, Adam Sherrard, and Kristina Boyer Pediatrics 2007; 119: 226. ERRATA ERRATA Pediatrics 2007; 119: 227. EXPERIENCE&REASON T-Cell–Based Diagnosis of Neonatal Multidrug- Resistant Latent Tuberculosis Infection LucaRicheldi,MD,PhDa,KatieEwer,PhDb,MonicaLosi,PhDa,BarbaraM.Bergamini,MDa,KerryMillington,BScb,c,LeonardoM.Fabbri,MDa, AjitLalvani,FRCP,DMb,c aDepartmentsofRespiratoryDiseaseandPediatrics,UniversityofModenaandReggioEmilia,Modena,Italy;bTuberculosisImmunologyGroup,NuffieldDepartmentof ClinicalMedicine,UniversityofOxford,JohnRadcliffeHospital,Oxford,UnitedKingdom;cTuberculosisImmunologyGroup,DepartmentofRespiratoryMedicine,National HeartandLungInstitute,WrightFlemingInstituteofInfectionandImmunity,ImperialCollegeLondon,London,UnitedKingdom FinancialDisclosure:DrLalvaniisanamedinventoronpatentsrelatingtoT-cell–baseddiagnosisfiledbytheUniversityofOxford.RegulatoryapprovalandcommercializationofELISpot(T-SPOT.TB)hasbeen undertakenbyaspin-offcompanyoftheUniversityofOxford(OxfordImmunotecLtd,Oxford,England),inwhichDrLalvanihasashareofequityandtowhichheactsasscientificadvisorinanonexecutive capacity.DrEwerisanamedinventoronapatentapplicationrelatingtotheapplicationofELISpotfiledbytheUniversityofOxford.TheUniversityofOxfordhasashareofequityinOxfordImmunotecLtd. ABSTRACT Youngchildrenexposedtotuberculosishaveahighriskofprogressiontoseveretuberculosisdisease,butdiagnosis ofrecentinfectionishinderedbythepoorsensitivityofthetuberculinskintest.Whethernewbloodtestscandetect latentinfectioninthisvulnerablegroupisunknownbecausethereisnogoldstandard.Wemonitoredatuberculin skintest–negativeinfantwhosemotherhadinfectiousmultidrug-resistanttuberculosiswithenzyme-linkedimmu- nospot,abloodtestthatenumeratesMycobacteriumtuberculosis–specificTcells.Theenzyme-linkedimmunospottest became persistently positive by 6 months, and 18 months later the child developed active tuberculosis despite appropriatechemoprophylaxis.Atthispoint,themagnitudeoftheenzyme-linkedimmunospotresponseincreased (cid:1)10-fold.Ourfindingsdemonstratethatthisbloodtestdetectedlatentinfectionwithdormant,yetviable,bacilliand illustrate how enzyme-linked immunospot could improve diagnosis of childhood tuberculosis infection. T HECURRENTSTRATEGYoftargetedtuberculintesting individual interferon-(cid:1)–producing T cells (T-SPOT.TB, andtreatmentoflatenttuberculosisinfection(LTBI) Oxford Immunotec Ltd, Abingdon, United Kingdom) is isaimedathigh-riskgroups,includingHIV-infectedpeo- approved for use in Europe and Canada and is being ple, people on immunosuppressive medication, and evaluatedbytheUSFoodandDrugAdministration;this young children.1 Unfortunately, it is precisely these assay has higher diagnostic sensitivity than the TST in groups in whom the tuberculin skin test (TST) is least children with active tuberculosis, particularly children reliable, because the results are frequently false-nega- younger than 3 years.8 Moreover, in a large school tu- tive.2Themostvulnerablegroupcomprisesinfantsaged berculosis outbreak, ELISpot results correlated more under 1 year, whose risk of progression after Mycobacte- closelywithMtuberculosisexposurethantheHeafintra- rium tuberculosis infection is (cid:1)50%.3,4 The TST can be dermal test, suggesting that it is also more sensitive for falsely negative in active tuberculosis and LTBI, but the detecting LTBI.9 However, in the absence of a gold- false-negativerateinLTBIcannotbecalculatedbecause standardtestforlatentinfection,itisdifficulttoconfirm of the absence of a gold-standard test.5 A recent review ofneonatalexposuretotuberculosisinNorthAmerican KeyWords:tuberculosis,neonate,diagnosis,ELISpot neonatal units found that none of the 2635 newborns Abbreviations:LTBI,latenttuberculosisinfection;TST,tuberculinskintest;ELISpot, developed a positive skin test.6 We believe that it is enzyme-linkedimmunospot;MDR,multidrug-resistant;PPD,purifiedprotein derivative;ESAT-6,earlysecretoryantigenictarget6;CFP10,culturefiltrateprotein10; unlikely that none of the newborns would have ac- SKSD,streptokinase-streptodornase;SFC,spot-formingcell quiredinfectionandassumethatthelackofanypositive www.pediatrics.org/cgi/doi/10.1542/peds.2006-1057 skin-testresultssuggeststhattheTSThaslowsensitivity in this age group. doi:10.1542/peds.2006-1057 Newrapidbloodtests,basedondetectionofinterfer- AcceptedforpublicationAug2,2006 AddresscorrespondencetoAjitLalvani,FRCP,DM,TuberculosisImmunologyGroup,WrightFleming on-(cid:1) released by T cells in response to M tuberculosis InstituteofInfectionandImmunity,NationalHeartandLungInstitute,ImperialCollegeLondon, antigens,offeranovelapproachtodiagnosingLTBI.7An NorfolkPlace,LondonW21NY,UnitedKingdom.E-mail:[email protected] PEDIATRICS(ISSNNumbers:Print,0031-4005;Online,1098-4275).Copyright©2007bythe enzyme-linkedimmunospot(ELISpot)assaythatdetects AmericanAcademyofPediatrics PEDIATRICSVolume119,Number1,January2007 e1 whetherinfants,andotherhigh-riskgroups,withapos- formed consent. Accordingly, the child had an ELISpot itiveELISpotresultsandanegativeTSTresulttrulyhave test,TST,andclinicalreviewattheageof11weeksand LTBI.Onlyprogressiontoactivetuberculosiscanprovide again at 6, 12, 18, and 24 months of age. definitive evidence that ELISpot detects LTBI when the TSTfailstodoso,buttherearenoreportedexamplesof METHODS this.HerewereporttheapplicationofELISpotfordiag- The TST was administered by the Mantoux method us- nosis of LTBI in a neonate born to a mother with un- ing 5 IU of purified protein derivative-Siebert (Biocine treated multidrug-resistant (MDR) tuberculosis. TestPPD,ChironCorporation/Sclavo,Siena,Italy).PPD- Siebert(ortuberculinPPD,lotnumber49608)istheUS CASEREPORT standard for all PPD preparations, which are standard- A24-year-oldwomanfromMoldovadeliveredahealthy ized against this product. The transverse diameter of infant at the University Hospital of Modena, Italy. One cutaneous induration was measured with a ruler and week after delivery, chest radiography strongly sug- recorded 72 hours after inoculation, using 5 mm as the gested active tuberculosis (Fig 1A). Three sputum sam- cutoff for a positive test.2 TSTs were placed and read by pleswerestronglypositiveforacid-fastbacilli.Standard an experienced pulmonologist who routinely looks 4-drugantituberculoustherapywasstarted,andshewas after patients with tuberculosis and who was blinded separated from her infant. Three weeks later, her spu- to the ELISpot results. The cutaneous appearance of tum specimens grew M tuberculosis that was resistant to peau d’orange was noted, confirming intradermal inoc- isoniazidandrifampinbutsensitivetopyrazinamideand ulation of PPD. No specific measures were used to pre- ethambutol.Afterswitchingtoa5-drugregimen(pyra- vent terminal rounding of the induration measure- zinamide, moxifloxacin, ethambutol, streptomycin, and ments. The ELISpots were performed as described clofazimine), the woman progressively improved. previously by using recombinant early secretory anti- Herasymptomatic4-week-oldinfanthadbeeninten- genic target 6 (ESAT-6), recombinant culture filtrate sively exposed during the 11 days from birth until the protein10(CFP10),and6poolsofoverlappingpeptides mother’shospitaladmission.Chestradiographyandme- derivedfromtheseantigens(3poolsofpeptidesforeach diastinalultrasoundwerenormal,andtheTSTwasneg- antigen).11 Mitogen-stimulated positive control wells ative. The infant did not receive BCG vaccination and containedphytohemagglutinin(ICNBiomedicals,Solon, was given 9 months of chemoprophylaxis with etham- OH), and antigen-stimulated positive control wells con- butol (15 mg/kg daily) and pyrazinamide (20 mg/kg tained streptokinase-streptodornase (SKSD; Wyeth daily) with directly observed therapy, consistent with FarmaSA,Madrid,Spain)asanindexofMtuberculosis– CentersforDiseaseControlandPreventionguidelines.10 unrelatedantigen-specificT-cellresponsiveness.ELISpot RecognizingthattheTSTresultmightbefalse-negative, plates were scored by an automated counter (AID- weofferedsupplementaryELISpottestingwithinapro- GmbH, Strasburg, Germany).11 All test conditions were tocolapprovedbytheModenaUniversityHospitalInsti- in duplicate wells, each of which contained 250000 tutional Review Board, and the parents provided in- peripheral blood mononuclear cells. Pairs of wells con- FIGURE1 A,Chestradiographoftheindexcase.Extensivepatchyconsol- idationwithareasofcavitationisseeninthemiddleandupper zones,consistentwithactivetuberculosis.B,Chestradiograph ofthechildat24monthsofage,thetimeatwhichhepre- sentedwithfeverandrespiratorysymptoms,showingright- sided hilar lymphadenopathy and ipsilateral parenchymal compression.C,Molecularstraintyping(DNAfingerprinting) using insertion sequence 6110 restriction fragment length polymorphism(RFLP)analysis(IS6110-basedRFLP)oftheMDR Mtuberculosisisolatesobtainedfromthemother’ssputumin November2001(upper)andfromherchild’sgastricaspiratein December2003(lowerlane).TheIS6110RFLPpatternsare identical,indicatingthatthemotherandchildwereinfected withthesamestrain. e2 RICHELDIetal

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Patricia van den Berg, Dianne Neumark-Sztainer, Peter J. Hannan, and Jess Haines Infection in the First 2 Years of Life and Autism Spectrum Disorders . Hallman, Sture Andersson, Mika Gissler, Jaana Leipälä, Outi Tammela, Unto Häkkinen for the PERFECT a positive or negative test result for gr
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