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syndrome of reconstitution immune in Children

Lisa Frigati, Moherdran Archary, Helena Rabie, Martina Penazzato, Nathan Ford
Early mortality and morbidity remain high in children initiating antiretroviral therapy (ART), especially in sub-Saharan Africa. Many children still present with advanced human immunodeficiency virus (HIV) disease. Tuberculosis, pneumonia, and severe bacterial infections are the main causes of hospital admission in HIV-infected children. In contrast to adults with advanced HIV disease, cryptococcal disease is not common in childhood, although there is a peak in infancy and adolescence. Interventions such as TB screening in symptomatic children, and isoniazid and cotrimoxazole prophylaxis should be implemented...
March 4, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Alice Bonanni, Marta Calatroni, Matteo D'Alessandro, Sara Signa, Enrica Bertelli, Michela Cioni, Eddi Di Marco, Roberto Biassoni, Gianluca Caridi, Giulia Ingrasciotta, Roberta Bertelli, Armando Di Donato, Maurizio Bruschi, Alberto Canepa, Giorgio Piaggio, Pietro Ravani, Gian Marco Ghiggeri
AIMS: Anti-CD20 antibodies are increasingly being used to treat idiopathic nephrotic syndrome (INS) in children. While they may allow steroid and calcineurin inhibitor withdrawal, repeated infusions of anti-CD20 antibodies are often required to maintain remission. Data on their potential toxicity in INS are needed, to consider repeated infusions. METHODS: We investigated the side effects associated with the use of rituximab (a chimeric antibody; 130 patients) and ofatumumab (a humanized antibody; 37 patients) in children with INS (steroid-dependent and steroid/calcineurin inhibitor-dependent disease) treated at a national referral centre over a 9-year period (400 treatments; follow-up 1-9 years)...
February 13, 2018: British Journal of Clinical Pharmacology
Irene N Njuguna, Lisa M Cranmer, Vincent O Otieno, Cyrus Mugo, Hellen M Okinyi, Sarah Benki-Nugent, Barbra Richardson, Joshua Stern, Elizabeth Maleche-Obimbo, Dalton C Wamalwa, Grace C John-Stewart
BACKGROUND: Urgent antiretroviral therapy (ART) among hospitalised HIV-infected children might accelerate recovery or worsen outcomes associated with immune reconstitution. We aimed to compare urgent versus post-stabilisation ART among hospitalised HIV-infected children in Kenya. METHODS: In this unmasked randomised controlled trial, we randomly assigned (1:1) HIV-infected, ART-naive children aged 0-12 years who were eligible for treatment to receive ART within 48 h (urgent group) or in 7-14 days (post-stabilisation group) at four hospitals in Kenya (two in Nairobi and two in western Kenya)...
January 2018: Lancet HIV
Jennifer Heimall, Brent R Logan, Morton J Cowan, Luigi D Notarangelo, Linda M Griffith, Jennifer M Puck, Donald B Kohn, Michael A Pulsipher, Suhag Parikh, Caridad Martinez, Neena Kapoor, Richard O'Reilly, Michael Boyer, Sung-Yun Pai, Frederick Goldman, Lauri Burroughs, Sharat Chandra, Morris Kletzel, Monica Thakar, James Connelly, Geoff Cuvelier, Blachy J Davila Saldana, Evan Shereck, Alan Knutsen, Kathleen E Sullivan, Kenneth DeSantes, Alfred Gillio, Elie Haddad, Aleksandra Petrovic, Troy Quigg, Angela R Smith, Elizabeth Stenger, Ziyan Yin, William T Shearer, Thomas Fleisher, Rebecca H Buckley, Christopher C Dvorak
The Primary Immune Deficiency Treatment Consortium (PIDTC) is enrolling children with severe combined immunodeficiency (SCID) to a prospective natural history study. We analyzed patients treated with allogeneic hematopoietic cell transplantation (HCT) from 2010 to 2014, including 68 patients with typical SCID and 32 with leaky SCID, Omenn syndrome, or reticular dysgenesis. Most (59%) patients were diagnosed by newborn screening or family history. The 2-year overall survival was 90%, but was 95% for those who were infection-free at HCT vs 81% for those with active infection ( P = ...
December 21, 2017: Blood
Melissa Norman, Clementine David, Brynn Wainstein, John B Ziegler, Richard Cohn, Richard Mitchell, Tracey O'Brien, Susan Russell, Toby Trahair, Annette Trickett, Katie Frith, Paul Gray
AIM: Haematopoietic stem cell transplantation (HSCT) is a central therapy in the treatment of primary immunodeficiency diseases (PIDs). Over the past 5 years, outcomes have been greatly improved due to earlier diagnosis, improved donor availability, advancements in graft manipulation and the use of less toxic preparative regimens. We present a 5-year audit of HSCT for PID at a single Australian tertiary hospital. METHODS: Retrospective case note review identified diagnosis, pre-transplant medical morbidity, transplant protocol, engraftment, adverse events, post-transplant immune reconstitution and general health...
July 28, 2017: Journal of Paediatrics and Child Health
Ashutosh Gupta, Suman Kushwaha, Mushbiq Manzoor, Shah Faisal Ahmad Tarfarosh
We report a 12-year-old boy with human immunodeficiency virus (HIV) who presented with rapidly progressive difficulty in ambulation. The symptoms started to worsen when he was put on antiretroviral therapy (ART). Our findings show that the dynamics of HIV-related immune suppression and highly active antiretroviral therapy (HAART) have an impact on the clinical course of Subacute sclerosing panencephalitis (SSPE). Slow progression is expected in children on HAART but in our case, we observe a complex interaction of the virus with the immune system and modification of disease course of SSPE with ART...
June 13, 2017: Curēus
Karina Jordan, Peter Pontoppidan, Hilde H Uhlving, Katrine Kielsen, Douglas G Burrin, Sarah Weischendorff, Ib J Christensen, Marianne H Jørgensen, Carsten Heilmann, Henrik Sengeløv, Klaus Müller
Liver toxicity is frequently seen in relation to allogeneic hematopoietic stem cell transplantation (HSCT), but pathogenesis and the risk factors are poorly understood. The purpose of this study was to investigate associations between liver toxicity, gastrointestinal toxicity, and levels of immune-regulating cytokines during the early post-transplantation period. We prospectively included 81 children and adults undergoing HSCT after myeloablative conditioning. Alanine aminotransferase (ALT), total bilirubin levels, and international normalized ratio were measured longitudinally until 3 months after the transplantation and related to levels of inflammatory markers (C-reactive protein [CRP], IL-6, and IL-10) and to plasma citrulline as a marker of intestinal toxicity during the first 3 weeks after HSCT...
July 2017: Biology of Blood and Marrow Transplantation
Isabelle Viel-Thériault, Roseline Thibeault, Francois D Boucher, Jean-Philippe Drolet
Paradoxical immune reconstitution inflammatory syndrome is a well-described entity even in immunocompetent children, principally in association with Mycobacterium tuberculosis infections. Central nervous system involvement is a potential life-threatening form, sometimes refractory to standard treatment. We report the case of an HIV-negative refugee teenager, who presented with brain tuberculomas and pseudoabscesses responsive only to thalidomide.
November 2016: Pediatric Infectious Disease Journal
Noella Maria Delia Pereira, Ira Shah, Shilpa Kulkarni
Opsoclonus-myoclonus-ataxia (OMA) syndrome typically presents with chaotic eye movements and myoclonus with some patients exhibiting ataxia and behavioural disturbances. The pathogenesis may be inflammatory with an infectious or paraneoplastic trigger. We present a 13-year-old HIV-infected girl who was initially started on highly active antiretroviral therapy (HAART) in March 2013 with a CD4 count of 79 cells/cumm. Initially, the patient did not comply with treatment, resulting in a CD4+ count of 77 cells/mm(3) in November 2015 and prompting a new HAART scheme comprising lamivudine, tenofovir and ritonavir-boosted atazanavir...
October 2016: Oxford Medical Case Reports
Claire Dossier, Agnès Jamin, Georges Deschênes
Steroid sensitive nephrotic syndrome is marked by a massive proteinuria and loss of podocytes foot processes. The mechanism of the disease remains debated but recent publications suggest a primary role of Epstein-Barr Virus (EBV). EBV replication in the peripheral blood is found in 50% of patients during the first flare of the disease. The genetic locus of steroid sensitive nephrotic syndrome was also identified as influencing antibodies directed against EBNA1. EBV is able to establish, latent benign infection in memory B cells that display phenotypes similar to antigen-selected memory B cells...
January 2017: Pediatric Research
Isabelle Viel-Thériault, Roseline Thibeault, Francois D Boucher, Jean-Philippe Drolet
Paradoxical immune reconstitution inflammatory syndrome (IRIS) is a well described entity even in immunocompetent children, principally in association with Mycobacterium tuberculosis infections. Central nervous system involvement is a potential life-threatening form, sometimes refractory to standard treatment. We report the case of an HIV-negative refugee teenager, who presented with brain tuberculomas and pseudo-abscesses responsive only to thalidomide.
June 21, 2016: Pediatric Infectious Disease Journal
Sharon Nachman, Carmelita Alvero, Edward P Acosta, Hedy Teppler, Brenda Homony, Bobbie Graham, Terence Fenton, Xia Xu, Matthew L Rizk, Stephen A Spector, Lisa M Frenkel, Carol Worrell, Edward Handelsman, Andrew Wiznia
BACKGROUND: IMPAACT P1066 is a Phase I/II open-label multicenter trial to evaluate safety, tolerability, pharmacokinetics (PK), and efficacy of multiple raltegravir (RAL) formulations in human immunodeficiency virus (HIV)-infected youth. METHODS: Dose selection of the oral suspension formulation for each cohort (IV: 6 months to <2 years and V: 4 weeks to <6 months) was based on review of short-term safety (4 weeks) and intensive PK evaluation. Safety data through Weeks 24 and 48 and Grade ≥3 or serious adverse events (AEs) were assessed...
December 2015: Journal of the Pediatric Infectious Diseases Society
Dmitry Balashov, Anna Shcherbina, Michael Maschan, Pavel Trakhtman, Yulia Skvortsova, Larisa Shelikhova, Alexandra Laberko, Anna Livshits, Galina Novichkova, Alexei Maschan
The transplantation of stem cells from a matched unrelated donor (MUD) or a haploidentical mismatched related donor (MMRD) is a widely used variant of curative treatment for patients with primary immunodeficiency (PID). Currently, different strategies are used to reduce the risk of post-transplant complications and enhance immune reconstitution. We report the preliminary results of MUD and MMRD transplantation with TCRαβ/CD19 depletion in patients with PID (trial registered at as NCT02327351)...
November 2015: Biology of Blood and Marrow Transplantation
Annelies Van Rie, Shobna Sawry, Ruth Link-Gelles, Shabir Madhi, Lee Fairlie, Charl Verwey, Nasreen Mahomed, David Murdoch, Harry Moultrie
BACKGROUND: Paradoxical tuberculosis (TB)-associated Immune Reconstitution Inflammatory Syndrome (IRIS) is a common complication of combination antiretroviral treatment (cART) initiation in adults residing in resource-limited regions. Little is known about the burden and presentation of TB-IRIS in children initiating cART while receiving TB treatment. METHODS: Prospective cohort study of South African children initiating cART while on TB treatment. Children were assessed clinically and by chest x-ray before starting cART and at 2, 4, 6, and 12 weeks post cART initiation...
February 2016: Pediatric Pulmonology
Alessia Scarselli, Silvia Di Cesare, Claudia Capponi, Simona Cascioli, Maria L Romiti, Gigliola Di Matteo, Alessandra Simonetti, Paolo Palma, Andrea Finocchi, Barbarella Lucarelli, Rita M Pinto, Ippolita Rana, Giuseppe Palumbo, Maurizio Caniglia, Paolo Rossi, Rita Carsetti, Caterina Cancrini, Alessandro Aiuti
PURPOSE: Hematopoietic cell transplantation (HCT) provides a curative therapy for severe forms of primary immunodeficiencies (PID). While the timing and extent of T-cell reconstitution following transplant for PID has been studied in depth, less is known about the kinetics of B-cell development and long-term restoration of humoral functions, which been often reported to be suboptimal after HCT. METHODS: We studied longitudinally B-cell development and function in a cohort of 13 PID patients transplanted between 1997 and 2010, with a follow-up ranging from 0...
May 2015: Journal of Clinical Immunology
Thomas Schneider, Verena Moos
Within the last years the understanding of infection with Tropheryma whipplei was significantly enhanced by improvement of molecular biology, microbiology and immunology. The following entities of infection or carriage, respectively, with T. whipplei must be differentiated: besides in the context of classical Whipple's disease (CWD), the rare chronic infection with T. whipplei (estimated incidence: 1 : 1,000,000), T. whipplei can be detected more frequently in stool specimens of children with acute gastroenteritis or asymptomatic carriers, or as a cause of isolated endocarditis...
March 2015: Deutsche Medizinische Wochenschrift
Janet Leath Alexander, Marijean Miller
Frosted branch angiitis is a rare vascular reaction believed to be a nonspecific immune response to an infective, neoplastic, or idiopathic insult. The clinical presentation is characteristic and typically affects children and younger adults, and the prognosis is good. We report a case of frosted branch angiitis during immune recovery in a 2-year-old boy with Langerhans cell histiocytosis on systemic immunosuppressive therapy.
February 2015: Journal of AAPOS: the Official Publication of the American Association for Pediatric Ophthalmology and Strabismus
Renate A Richardus, C Ruth Butlin, Khorshed Alam, Kallyan Kundu, Annemieke Geluk, Jan Hendrik Richardus
BACKGROUND: Although BCG is used as a vaccine against tuberculosis, it also protects against leprosy. Previous evaluation over 18 years of an intervention of two doses BCG for 3536 household contacts of leprosy patients showed that 28 (23%) out of 122 contacts diagnosed with leprosy, developed symptoms 2-10 months after vaccination. This study describes contacts of leprosy patients in Bangladesh who developed leprosy within 12 weeks after receiving a single BCG dose. METHODS: A cluster RCT in Bangladesh aims to study the effectiveness of the BCG vaccine versus BCG in combination with single dose rifampicin (SDR) given 2 to 3 months after BCG, in the prevention of leprosy among contacts of newly diagnosed leprosy patients...
March 24, 2015: Vaccine
M C Elze, O Ciocarlie, A Heinze, S Kloess, T Gardlowski, R Esser, T Klingebiel, P Bader, S Huenecke, M Serban, U Köhl, J L Hutton
DCs are potent APCs and key regulators of innate and adaptive immunity. After allo-SCT, their reconstitution in the peripheral blood (PB) to levels similar to those in healthy individuals tends to be slow. We investigate the age- and sex-dependant immune reconstitution of myeloid (mDC) and plasmacytoid DC (pDC) in the PB of 45 children with leukaemia or myelodysplastic syndrome (aged 1-17 years, median 10) after allo-SCT with regard to relapse, acute GVHD (aGVHD) and relapse-free survival. Low pDC/μL PB up to day 60 post SCT are associated with higher incidence of moderate or severe aGVHD (P=0...
February 2015: Bone Marrow Transplantation
Margot R Krauss, D Robert Harris, Thalita Abreu, Fabiana G Ferreira, Noris Pavia Ruz, Carol Worrell, Rohan Hazra
OBJECTIVE: To evaluate the occurrence, clinical presentations and diagnostic methods for tuberculosis in a cohort of HIV-infected infants, children and adolescents from Latin America. METHODS: A retrospective analysis of children with tuberculosis and HIV was performed within a prospective observational cohort study conducted at multiple clinical sites in Latin America. RESULTS: Of 1114 HIV-infected infants, children, and adolescents followed from 2002 to 2011, 69 that could be classified as having confirmed or presumed tuberculosis were included in this case series; 52...
January 2015: Brazilian Journal of Infectious Diseases
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