Publications

27

Sep, 2019

The challenge of the laboratory diagnosis in a confirmed congenital Zika virus syndrome in utero: a case report

 

Authors: Sulleiro E, Frick MA, Rodó C, et al.

Published in: Medicine (Baltimore). 2019;98(20):e15532

Introduction Zika virus (ZIKV) has caused one of the most challenging global infectious epidemics in recent years because of its causal association with severe microcephaly and other congenital malformations. The diagnosis of viral infections usually relies on the detection of virus proteins or genetic material in clinical samples as well as on the infected host immune responses. Serial serologic testing is required for the diagnosis of congenital infection when diagnostic molecular biology is not possible.

Patient concerns A 2-year-old girl, born to a mother with confirmed ZIKV infection during pregnancy, with a confirmed ZIKV infection in utero, showed at birth a severe microcephaly and clinical characteristics of fetal brain disruption sequence compatible with a congenital ZIKV syndrome (CZS).

Diagnosis ZIKV-RNA and ZIKV-IgM serological response performed at birth and during the follow-up time tested always negative. Serial serologic ZIKV-IgG tests were performed to assess the laboratory ZIKV diagnosis, ZIKV-IgG seroreversion was observed at 21 months of age. ZIKV diagnosis of this baby had to be relied on her clinical and radiological characteristics that were compatible with a CZS.

Interventions The patient was followed-up as per protocol at approximately 1, 4, 9, 12, 18-21, and 24 months of age. Neurological, radiological, audiological, and ophthalmological assessment were performed during this period of time. Prompt rehabilitation was initiated to prevent potential adverse long-term neurological outcomes.

Outcomes The growth of this girl showed a great restriction at 24 months of age with a weight of 8.5 kg (-2.5 z-score) and a head circumference of 40.5 cm (-4.8 z-score). She also had a great neurodevelopmental delay at the time of this report.

Conclusions We presume that as a consequence of prenatal ZIKV infection, the fetal brain and other organs are damaged before birth through direct injury. Following this, active infection ends during intrauterine life, and as a consequence the immune system of the infant is unable to build up a consistent immune response thereafter. Further understanding of the mechanisms taking part in the pathogenesis of ZIKV congenital infection is needed. This finding might change our paradigm regarding serological response in the ZIKV congenital infection.

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27

Sep, 2019

Let’s talk about antimicrobial resistance: Penta at European Researchers’ Night

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Penta will be at the European Researchers’ Night in Padua on 27 September, 2019. For this edition we have chosen the theme of ‘antimicrobial resistance’ (AMR). With the help of flyers and an educational video we hope to illustrate to the public what ‘AMR’ is, how it develops and spreads, and raise awareness on how much this problem is threatening global health. Our team will point out some simple yet extremely important practices that can help limit the rise of resistance.

Antimicrobials are one of the most important fields of activity for Penta; we are involved in several European and global initiatives aimed at better characterizing the use of antibiotics among children and neonates, the scale of resistance in this population and at investigating optimal treatment regimens for common neonatal infections.

The European Researchers’ Night is an initiative that, since 2005, has brought together researchers and the general public in different European cities on the same date in late summer: the fourth Friday in September. The event is a unique opportunity to invite the public to explore the world of research, to open a space for meeting and starting a dialogue with citizens and to encourage young people to pursue scientific careers. People of all ages will have the opportunity to visit research facilities that are usually not open to the public, use the latest technologies with the guidance of researchers, participate in experiments, competitions, demonstrations and simulations, exchange ideas and, most of all, have fun!

25

Sep, 2019

Uniting against antibiotic resistance: ‘5 by 25’

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Our friends at GARDP are calling upon the global community to support its goal to develop and deliver five new treatments by 2025 in response to the growing burden of antibiotic resistant infections.

Antibiotics have radically transformed our world by making previously incurable illnesses treatable. As a result, not only has our wellbeing significantly improved, but millions of lives have been saved. However, this remarkable progress is threatened by the spread of antibiotic resistance and requires an urgent global response.

We need solutions that will deliver for global public health. No one country or sector can do it alone. The GARDP model of public-private partnerships is key to preventing the world form entering a post-antibiotic era. Only together can we tackle this impending crisis!

GARDP invite you to join them at this year’s World Health Summit in Berlin to learn how their ‘5 BY 25’ goal will accelerate the development and delivery of five new and improved treatments to address antibiotic-resistant infections that pose the greatest threat to health and development. These new treatments will focus on the priority pathogens identified by the World Health Organization, and current unmet needs for diseases and key populations.

If you are interested in attending please write to ‘contact@gardp.org‘ by 17 October 2019.

 

Event details:

Date: Monday 28 October, 2019
Time: 14.00 –15:30
Venue: Saal 2 – America, Kosmos, Karl-Marx-Allee 131a, Berlin, Germany

24

Sep, 2019

Non-inferiority double-blind randomised controlled trial comparing gabapentin versus tramadol for the treatment of chronic neuropathic or mixed pain in children and adolescents: the GABA-1 trial-a study protocol

 

Authors: Kaguelidou F, Le Roux E, Mangiarini L, et al.; GAPP consortium

Published in: BMJ Open. 2019;9(2):e023296

Introduction Gabapentin is currently used ‘off-label’ in children and adolescents with chronic neuropathic pain, and reliable evidence of its effects and optimal dosing are lacking.

Objectives The GABA-1 trial aims to compare the efficacy and safety of gabapentin liquid formulation relative to tramadol and to explore the pharmacokinetics of both drugs in the treatment of chronic, neuropathic or mixed pain in the paediatric population.

Methods and analysis The trial is a multicentre, double-blind, double-dummy, randomised, active-controlled, non-inferiority trial. Participants aged from 3 months to <18 years of age with moderate to severe (≥4/10 in age-appropriate pain scales) chronic neuropathic or mixed pain will be recruited in 14 clinical sites in eight European countries. A total of 94 subjects will be randomised to receive gabapentin and tramadol placebo or tramadol and gabapentin placebo throughout 16–19 weeks (including 3 weeks of titration [optimisation period], 12 weeks of treatment at a stable dose [maintenance period] and 1–4 weeks of tapering [discontinuation period]). The primary objective is to assess the efficacy of gabapentin relative to tramadol for the treatment of moderate to severe chronic neuropathic or mixed pain by comparing the difference in average pain scores (assessed by age-appropriate pain scales) between intervention arms after 15 weeks of treatment. Secondary objectives include the assessment of the safety, quality of life and global satisfaction with treatment and the description of the pharmacokinetic–pharmacodynamic relationship of gabapentin liquid formulation and tramadol oral drops to validate the recommended paediatric doses. Only rescue pain medication by paracetamol and/or ibuprofen is allowed during the trial.

Ethics and dissemination Ethic approval was obtained in the eight participating countries. Results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences.

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24

Sep, 2019

Gabapentin as add-on to morphine for severe neuropathic or mixed pain in children from age 3 months to 18 years – evaluation of the safety, pharmacokinetics, and efficacy of a new gabapentin liquid formulation: study protocol for a randomized controlled trial

 

Authors: de Leeuw TG, Mangiarini L, Lundin R, et al; GAPP consortium

Published in: Trials. 2019; 20(1):368

Background Gabapentin has shown efficacy in the treatment of chronic neuropathic or mixed pain in adults. Although pediatric pain specialists have extensive experience with gabapentin for the treatment of neuropathic pain, its use is off-label. Its efficacy and safety in this context have never been shown. The aim of this trial is to compare gabapentin with placebo as add-on to morphine for the treatment of severe chronic mixed or neuropathic pain in children. This trial is part of the European Union Seventh Framework Programme project Gabapentin in Paediatric Pain (GAPP) to develop a pediatric use marketing authorization for a new gabapentin suspension.

Methods/design The GAPP-2 study is a randomized, double-blind, placebo-controlled, multicenter superiority phase II study in children with severe chronic neuropathic or mixed pain. Its primary objective is to evaluate the efficacy of a gabapentin liquid formulation as adjunctive therapy to morphine. Sixty-six eligible children 3 months to 18 years of age with severe pain (pain scores ≥ 7), stratified in three age groups, will be randomized to receive gabapentin (to an accumulating dose of 45 to 63 mg/kg/day, dependent on age) or placebo, both in addition to morphine, for 12 weeks. Randomization will be preceded by a short washout period, and treatment will be initiated by a titration period of 3 weeks. After the treatment period, medication will be tapered during 4 weeks. The primary endpoint is the average pain scores in the two treatment groups (average of two measures each day for 3 days before the end-of-study visit [V10] assessed by age-appropriate pain scales (Face, Legs, Activity, Cry, Consolability scale; Faces Pain Scale–Revised; Numeric Rating Scale). Secondary outcomes include percentage responders to treatment (subjects with 30% reduction in pain scale), number of episodes of breakthrough pain, number of rescue interventions, number of pain-free days, participant dropouts, quality of life (Pediatric Quality of Life Inventory), and acceptability of treatment. Outcomes will be measured at the end-of-study visit after 12 weeks of treatment at the optimal gabapentin dose. Groups will be compared on an intention-to-treat basis.

Discussion We hope to provide evidence that the combination of morphine and gabapentin will provide better analgesia than morphine alone and will be safe. We also aim to obtain confirmation of the recommended pediatric dose.

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17

Sep, 2019

Penta HIV 1st and 2nd Line Antiretroviral Treatment Guidelines 2019

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“The new updated edition of the Penta guidelines to support the use of ARVs in children is an essential contribution to paediatric patient care. Huge thanks to all those who participated in and led this work.” – Carlo Giaquinto

We are pleased to report that the 2019 Penta guidelines for first and second line antiretroviral treatment are now available. The aim of these guidelines is to provide an update to previous versions and are intended to guide antiretroviral choices for children and adolescents with perinatally acquired HIV in the European region.

The guidance will be updated at regular intervals by the Penta guidelines writing group or as significant new data or evidence becomes available.

You can download the guidelines here.

16

Sep, 2019

c4c pool of expert patients: get involved!

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c4c (conect4children) is a large collaborative European network that aims to facilitate the development of new drugs and other therapies for the entire paediatric population.

In this sense, the voices of children, young people and their families are a pivotal part of the innovative approach of c4c project. It places patients at the centre and will assign them an active role in the development of the different clinical trials that are going to be conducted during this project.

For this reason, and in order to guarantee patients’ involvement in all the activities of the project, c4c has setup a database to gather information on patients, caregivers, patient organizations and/or YPAGs (Young Person’s advisory boards) of rare/paediatric diseases.

If you wish (or know someone who could wish) to be part of the c4c pool of expert patients, you can find out more by following the instructions here!

14

Sep, 2019

Pharmacokinetics of dolutegravir 5mg dispersible tablets in children weighing 6 to <20kg dosed using WHO weight bands

 

Authors: Waalewijn H, Bollen PDJ, Moore C, Kekitiinwa A, et al. The ODYSSEY Trail Team

Published in: Oral Presentation at 10th IAS Conference, July, 21-24th 2019

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14

Sep, 2019

Follow up of Children with Confirmed Perinatal Zika Virus (ZIKV) Exposure: The First 2 years-experience in the Costa Rican Tertiary Pediatric Hospital

 

Authors: Tedder RS, Dicks S, Ijaz S, et al.

Published in: PLoS One. 2019;14(8):e0215708

Abstract The accurate diagnosis and seroprevalence investigations of Zika virus (ZKV) infections remain complex due to cross reactivity with other flaviviruses. Two assay formats, both using labelled Zika virus NS1 antigen as a revealing agent (a double antigen binding assay, DABA, and an immunoglobulin Ig capture assay, G capture) were initially developed and compared with the indirect EuroimmunZ assay for the detection of anti-Zika antibody. Of 147 pre-Zika period serum samples, 39 (27%) were reactive in the EuroimmunZ or the DABA assays, 28 sera concordantly so. Such false reactivity was influenced by the serotype of Dengue virus (DV) to which individuals had been exposed to. Thus, of sera from patients undergoing secondary Dengue virus infection of known serotype, 91%, 45% and 28% of Dengue virus serotype 2, 3 and 4 respectively were reactive in one or more of the three assays. A novel method of quenching false sero-reactivity was therefore developed for the DABA and G capture assays. Initial addition of a single homologous Dengue virus serotype 3 NS1Ag quench significantly ablated false reactivities in the pre-Zika period sera. An equipotent quadrivalent quench comprising homologous Dengue virus serotypes 1 to 4 NS1Ag was shown to be optimum yet retained sensitivity for the detection of specific anti-Zika antibody. Comparing DABA and G capture assays using quenched and unquenched conjugates in comparison with EuroimmunZ early in the course of PCR-confirmed infection indicated that a significant component of the apparent early anti-ZIKA antibody response is likely to be due to a Zika virus-driven anamnestic anti-Dengue virus response. The increased specificity provided by homologous antigen quenching is likely to provide a significant improvement in sero-diagnostics and to be of clinical value.

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9

Sep, 2019

Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus

 

Authors: Kraemer MUG, Reiner RC Jr, Brady OJ, et al.

Published in: Nat Microbiol. 2019;4:900

Abstract The global population at risk from mosquito-borne diseases—including dengue, yellow fever, chikungunya and Zika—is expanding in concert with changes in the distribution of two key vectors: Aedes aegypti and Aedes albopictus. The distribution of these species is largely driven by both human movement and the presence of suitable climate. Using statistical mapping techniques, we show that human movement patterns explain the spread of both species in Europe and the United States following their introduction. We find that the spread of Ae. aegypti is characterized by long distance importations, while Ae. albopictus has expanded more along the fringes of its distribution. We describe these processes and predict the future distributions of both species in response to accelerating urbanization, connectivity and climate change. Global surveillance and control efforts that aim to mitigate the spread of chikungunya, dengue, yellow fever and Zika viruses must consider the so far unabated spread of these mosquitos. Our maps and predictions offer an opportunity to strategically target surveillance and control programmes and thereby augment efforts to reduce arbovirus burden in human populations globally.

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