Publications

Authors: Palma P, McManus M, Cotugno N, Rocca S, Rossi P, Luzuriaga K

Published in: Lancet HIV. 2020;7(5):e359-e365

Authors: Soriano-Arandes A, Frick MA, García López-Hortelano M, et al.

Published in: Pathogens 2020;9(5):E352

Authors: Dhummakupt A, Rubens JH, Andeson T, et al.

Published in: JCI Insight. 2020;5(4)

Authors: Brice J, Sylla M, Desire N, Sayon S, Telly F, Bocar-Fofana D, Murphy R, Peytavin G, Diallo S, Nastouli E, Calvez V, Marcelin AG, Maiga AI, Lambert-Niclot S

Published in: The Journal of antimicrobial chemotherapy

Authors: L. Hill, E. Jacqz-Aigrain, V. Elie, W. Zhao, M. Clements, M. Turner, I. Lutsar, P. Heath, E. Roilides, S. Walker, M. Sharland

Published in: 30th European Congress on Clinical Microbiology and Infectious Diseases (ECCMID), April 2020

Authors: L. Hill, M. Clements, M. Turner, I. Lutsar, E. Jacqz-Aigrain, P. Heath, E. Roilides, S. Walker, M. Sharland

Published in: 30th European Congress on Clinical Microbiology and Infectious Diseases (ECCMID), April 2020

Authors: V. Matheeussen, K. Loens, K. Jacobs, P. Horby, H. Goossens, M. Kohns Vasconcelos, M. Sharland, M. De Jong, M. P. G. Koopmans, P. Fraaij, M. Ieven

Published in: 30th European Congress on Clinical Microbiology and Infectious Diseases (ECCMID), April 2020

Authors: M. Kohns Vasconcelos; on behalf of the PED-MERMAIDS Study Group

Published in: 30th European Congress on Clinical Microbiology and Infectious Diseases (ECCMID), April 2020

Authors: E. Barbieri, D. Bottigliengo, P. Costenaro, A. Marzollo, M. Petris, M. Pierobon, G. Biddeci, C. Giaquinto, A. Biffi, D. Donà

Published in: 30th European Congress on Clinical Microbiology and Infectious Diseases (ECCMID), April 2020

Authors: P. Costenaro, A. Cantarutti, E. Barbieri, A. Scamarcia, A. Oletto, P. Sacerdoti, R. Lundin, L. Cantarutti, C. Giaquinto, D. Dona’

Published in: 30th European Congress on Clinical Microbiology and Infectious Diseases (ECCMID), April 2020

Authors: Hill LF, Turner MA, Lutsar I, et al; NeoVanc Consortium.

Published in: Trials. 2020;21(1):329

Authors: Giovanetti M, Faria NR, Lourenco J, et al.

Published in:  Cell Rep. 2020;30(7):2275-2283

Authors: Dhummakupt A, Reubens JH, Anderson T, et al.

Published: Poster presented at 27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

Authors: Schröter J, Anelone A,  Yates A, de Boer RJ;  on behalf of the EPIICAL Consortium

Published in: J Acquir Immune Defic Syndr. 2020;83(5):522-529

Background Interventions aiming for an HIV cure would benefit from rapid elimination of virus after the onset of antiretroviral therapy (ART), by keeping the latent HIV reservoir small.

Setting We investigated HIV suppression in 312 perinatally infected infants starting ART within 6 months after birth from the EPPICC (European Pregnancy and Paediatric HIV Cohort Collaboration).

Methods To better understand kinetic differences in HIV suppression among infants, we investigated their individual viral load (VL) decay dynamics. We identified VL decay patterns and determined times to viral suppression (TTS). For infants with strictly declining VLs (n = 188), we used parameter fitting methods to estimate baseline VLs, decay rates, and TTS. We subsequently identified the parameters determining TTS by linear modeling.

Results The majority of infants suppress HIV VL after the onset of ART. Some children experienced a long TTS due to an “erratic” VL decay pattern. We cannot exclude that this is partly due to treatment complications and subsequent treatment changes, but these children were characterized by significantly lower CD4 percentages (CD4%) at start of treatment compared with those with a “clean” VL decline. Focusing on this “clean” subset, the TTS could be predicted by mathematical modeling, and we identified baseline VL and CD4% as the major factors determining the TTS.

Conclusions As VL steeply increases and CD4% constantly decreases in untreated HIV-infected infants, the progression of an HIV infection is largely determined by these 2 factors. To prevent a further disease progression, treatment should be initiated early after contracting HIV, which consequently shortens TTS.

Authors: Dominguez-Rodriguez S, Rojo P, Lain MG,  Barnabas S, Lopez-Varela E, Otwombe K, Danaviah S, Nastouli E, Serna-Pasqual M, Gianuzzi V, Giaquointo C, Kuhn L, Tagarro A on behalf of the EPIICAL Consortium

Published in: 27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

Authors: Sconza R, Plotnikova Y, Plynsky A, Rozenberg V, Thorne C

Published in: 10th International Workshop on HIV & Women, 6th – 7 th March 2020, Boston, MA

Authors: Crichton S, Jesson J, Aké-Assi MH, Belfrage E, Davies MA, Pinto J, Teasdale C, Van Lam N, Vreeman R, Wanless S, Williams P, Yotebieng M, Leroy V, Goodall R on behalf of the CIPHER Global Cohort Collaboration

Published in: 27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

Authors: Zicari S, Doria M, Domínguez-Rodríguez S, Cotugno N, Tagarro A, Rojo P, Nastouli E, Gartner K, Klein N, Foster C, Pahwa S, De Rossi A, Giaquinto C, Rossi P,  Palma P, for the EPIICAL consortium

Published in: 27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

Authors: Tagarro A, Domínguez-Rodríguez S, Violari A, Cotton M, Mhampossa T, Klein N, Ramsagar N, Van Rensburg AJ, Behuhuma O, Vaz P,  Oletto A, Palma P, Rossi P, Rojo P, on behalf of the EPIICAL Consortium

Published in:  27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

Authors: Gärtner K, Gkouleli T, Byott M, Heaney J, Spyer MJ, DeRossi A, Persaud D, Palma P, Giaquinto C, Rojo P, Foster C, Marcelin AG, Rossi P, Nastouli E, for the EPIICAL consortium

Published in:  27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

Authors: Gärtner K, Gkouleli T, Heaney J, Grant P, Dominguez-Rodriguez S, Busby E, O’Sullivan D, Spyer MJ, Foster C, Rojo P, Persaud D, DeRossi A, Huggett J, Nastouli E, for the EPIICAL consortium

Published in:  27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

Authors: Waalewijn H, Mujuru HA, Amuge P, Cotton M, Bollen P, Chan M, Ali S, Variavan E, Makumbi S, Colbers A, Gibb D, Ford D, Burger D, Turkova A, and the ODYSSEY-trial team

Published in:  27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

Authors: Waalewijn H, Mujuru HA, Amuge P, Cotton M, Bollen P, Chan M, Ali S, Variavan E,Makumbi S, Colbers A, Gibb D, Ford D, Burger D, Turkova A, and the ODYSSEY-trial team

Published in: Oral presentation at 27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

Authors: Crichton S , Collins  IJ, Turkova A, Ene L, Galli L, Marczynska M, Navarro M, Naver L, Noguera-Julian A, Plotnikova Y, Scherpbier H, Volokha A, Voronin E, Judd A; on behalf of the European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC)

Published in: 27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

Abstract

Background: The World Health Organization (WHO) recommends abacavir as the preferred/alternative backbone for 1st line regimens in children with HIV from age 28 days. There are limited data available on safety and tolerability of abacavir in young infants aged <3 months.

Methods: We describe infant and regimen characteristics at the start of abacavir (including drug combinations and dosing) and outcomes up to 12 months after first use of abacavir. Outcomes include:

• drug discontinuations (defined as interruption of abacavir for >30 days),
• clinical adverse events (AE, reported from start of abacavir, and up to 30 days after discontinuation of abacavir) and
• viral load at 6 and 12 (±3) months after start of abacavir

Conclusions: Across children initiating abacavir in early life in Europe, it was safe and well tolerated, and discontinuations for safety concerns were rare. • Viral suppression was below the UN-AIDS 90% target which may reflect challenges of treatment in infancy.

View poster

Authors: Thorne C, Rasi V, Aebi-Popp K, Ene L, Floridia M, Mendoza-Palomar N, Prieto L, Ragone L, Sconza R, CGiaquinto C, Vannappagari V; for the Dolomite-EPPICC study group

Published in: Oral presentation at 27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

Abstract

BACKGROUND • In 2018, the Tsepamo Study, Botswana reported significant increased risk of NTD in women conceiving on DTG (0.94%) 1 leading to a safety alert • Updated analysis of NTD prevalence (08/2014 – 03/2019)2 • 5 NTDs/1,683 deliveries in women on DTG at conception (0.30%, 95% CI 0.13-0.69 vs 0.10%, 95% CI 0.06-0.17 for non-DTG ART at conception • The Antiretroviral Pregnancy Registry recently reported 1 NTD in 312 periconception DTG exposures (0.3%) 3 • The Dolomite Study was set up in 2017 to address use & safety of DTG in pregnancy and exposed infants in Europe and Canada; conducted within the NEAT-ID network and EPPICC (the European Pregnancy and Paediatric Infections Cohort Collaboration)

Aim: To assess pregnancy and neonatal outcomes following DTG use during pregnancy in real-world European settings • Objectives were to describe: • characteristics of pregnant women receiving DTG-based regimens • frequency of adverse pregnancy and birth outcomes, by earliest timing of DTG exposure

Method: Dolomite-EPPICC involves pooled analyses of prospectively collected individual patient data on DTG-exposed pregnancies from participating studies • Data specification based on a modified HIV Data Exchange Protocol (www.hicdep.org) • Data merger included • All pregnancies with any prenatal DTG exposure • With birth outcomes reported by Feb 2019 • Periconception DTG exposure was defined as initial exposure at ≤6 weeks of estimated gestational age (EGA)

Results: 453 pregnancies in 428 women included (Figure) • Pregnancies reported from six countries • 347 (76.6%) UK and Ireland, 45 (9.9%) Spain, 29 (6.4%) Switzerland, 29 (6.4%) Italy, 3 (0.7%) Romania

View poster

Authors: Jackson C, Bamford A, Crichton S, Goodall R,Goulder P, Klein N, Marques L, Paioni P, Riordan A, Spoulou V, Vieira VA, Collins IJ. On behalf of The European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC) study group

Published in:  27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

Authors: Rinaldi S, Pallikkuth S, de Armas L, Pahwa R, Dominguez S, Cotugno N, Rojo Conejo P, Nastouli E, Gartner K, Klein N, Foster C, De Rossi A, Carlo Giaquinto C, Rossi P, Palma P, Pahwa S and EPIICAL Consortium

Published in:  27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

Authors: Lain MG, Vaz P, Ismael N,  Cantarutti A, Porcu G, Palma P, Cotugno N, Bila D, Rinaldi S,  Pallikkuth S, Pahwa R, Taibo E, Esmeralda Karajeanes E, Giaquinto C, Pahwa S.

Published in:  27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

Authors: Morris SE, Dziobek-Garrett L, Yates AJ and the EPIICAL consortium

Published in: BMC Bioinformatics 2020;21(1):52

Background HIV/AIDS is responsible for the deaths of one million people every year. Although mathematical modeling has provided many insights into the dynamics of HIV infection, there is still a lack of accessible tools for researchers unfamiliar with modeling techniques to apply them to their own clinical data.

Authors: Ades AE, Thorne C, Soriano-Arandes A, et al.

Published in: Lancet Infect Dis. 2020 Feb 18

Abstract: Our understanding of congenital infections is based on prospective studies of women infected during pregnancy. The EU has funded three consortia to study Zika virus, each including a prospective study of pregnant women. Another multi-centre study has been funded by the US National Institutes of Health. This Personal View describes the study designs required to research Zika virus, and questions whether funding academics in the EU and USA to work with collaborators in outbreak areas is an effective strategy. 3 years after the 2015–16 Zika virus outbreaks, these collaborations have taught us little about vertical transmission of the virus. In the time taken to approve funding, agree contracts, secure ethics approval, and equip laboratories, Zika virus had largely disappeared. By contrast, prospective studies based on local surveillance and standard-of-care protocols have already provided valuable data. Threats to fetal and child health pose new challenges for global preparedness requiring support for the design and implementation of locally appropriate protocols. These protocols can answer the key questions earlier than externally designed studies and at lower cost. Local protocols can also provide a framework for recruitment of unexposed controls that are required to study less specific outcomes. Other priorities include accelerated development of non-invasive tests, and longer-term storage of neonatal and antenatal samples to facilitate retrospective reconstruction of cohort studies.

Authors: Celia C.

Published in: Oral presentation at 3rd international Conference on Zika Virus and aedes related infections, February 13th – 16th, 2020– Washington DC, USA.

Authors: Webster-Kerr K.

Published in: Oral presentation at 3rd international Conference on Zika Virus and aedes related infections, February 13th – 16th, 2020– Washington DC, USA.

Authors: Lue A.

Published in: Oral presentation at 3rd international Conference on Zika Virus and aedes related infections, February 13th – 16th, 2020– Washington DC, USA.

Authors: Cotugno N, Morrocchi E, Rinaldi S, et al; EPIICAL Consortium.

Published in: AIDS. 2020 Feb 3.

Objective To investigate long-term persistence of HIV-specific lymphocyte immunity in perinatally HIV-infected children treated within the first year of life.

Design Twenty perinatally HIV-infected children who received ART therapy within the first year of life (early treated) and with stable viral control (>5 years) were grouped according to their serological response to HIV.

Methods Western blot analysis and ELISA defined 14 HIV-seropositive and 6 seronegative patients. Frequencies of gp140-specific T-cell and B-cell, and T-cell cytokine production were quantified by flow cytometry in both seronegatives and seropositives. Transcriptional signatures in purified gp140-specific B-cell subsets, in response to in-vitro stimulation with HIV peptides was evaluated by multiplex RT-PCR.

Authors: Warris A, Pana ZD, Oletto A, et al. EUROCANDY study group.

Published in: Pediatr Infect Dis J. 2020;39(2):114-120

Background Data on Candida bloodstream infections in pediatric patients in Europe are limited. We performed a retrospective multicenter European study of the epidemiology and outcome of neonatal and pediatric candidemia.

Materials and methods All first positive blood cultures from patients ≤ 18 years of age with candidemia were registered. Patients’ demographic and clinical characteristics and causative Candida species were collected and analyzed. Regression analysis was used to identify factors independently associated with mortality.

Results One thousand three hundred ninety-five episodes of candidemia (57.8% male) were reported from 23 hospitals in 10 European countries. Of the 1395 episodes, 36.4% occurred in neonates (≤ 44 weeks postmenstrual age), 13.8% in infants (> 44 weeks postmenstrual age to 1 year) and 49.8% in children and adolescents. Candida albicans (52.5%) and Candida parapsilosis (28%) were the predominant species. A higher proportion of candidemia caused by C. albicans was observed among neonatal patients (60.2%) with highest rates of C. parapsilosis seen among infants (42%). Children admitted to hematology-oncology wards presented the highest rates of non-albicans Candida species. Candidemia because of C. albicans was more frequent than non-albicans Candida in Northern versus Southern Europe (odds ratio, 2.3; 95% confidence interval, 1.8-2.9; P < 0.001). The all-cause mortality at 30 days was 14.4%. All-cause mortality was higher among patients admitted to the neonatal or pediatric intensive care units than other wards. Over time, no significant changes in species distribution were observed.

Conclusions This first multicenter European study shows unique characteristics of the epidemiology of pediatric candidemia. The insights obtained from this study will be useful to guide clinical management and antifungal stewardship.

Authors: Pereira Gusmão Maia Z, Mota Pereira F, do Carmo Said RF, et al.

Published in: Emerg Microbes Infect. 2020;9(1):53-57

Abstract Between June 2017 and August 2018, several municipalities located in Bahia state (Brazil) reported a large increase in the number of patients presenting with febrile illness similar to that of arboviral infections. Using a combination of portable whole genome sequencing, molecular clock and epidemiological analyses, we revealed the return of the CHIKV-ECSA genotype into Bahia. Our results show local persistence of lineages in some municipalities and the re-introduction of new epidemiological strains from different Brazilian regions, highlighting a complex dynamic of transmission between epidemic seasons and sampled locations. Estimated climate-driven transmission potential of CHIKV remained at similar levels throughout the years, such that large reductions in the total number of confirmed cases suggests a slow, but gradual accumulation of herd-immunity over the 4 years of the epidemic in Bahia after its introduction in 2014. Bahia remains a reservoir of the genetic diversity of CHIKV in the Americas, and genomic surveillance strategies are essential to assist in monitoring and understanding arboviral transmission and persistence both locally and over large distances.

Authors: Donà D, Barbieri E, Daverio M, Lundin R, Giaquinto C, Zaoutis T, Sharland M

Published in: Antimicrob Resist Infect Control.2020;9:3

Background Antibiotics are the most common medicines prescribed to children in hospitals and the community, with a high proportion of potentially inappropriate use. Antibiotic misuse increases the risk of toxicity, raises healthcare costs, and selection of resistance. The primary aim of this systematic review is to summarize the current state of evidence of the implementation and outcomes of pediatric antimicrobial stewardship programs (ASPs) globally.

Methods MEDLINE, Embase and Cochrane Library databases were systematically searched to identify studies reporting on ASP in children aged 0-18 years and conducted in outpatient or in-hospital settings. Three investigators independently reviewed identified articles for inclusion and extracted relevant data.

Results Of the 41,916 studies screened, 113 were eligible for inclusion in this study. Most of the studies originated in the USA (52.2%), while a minority were conducted in Europe (24.7%) or Asia (17.7%). Seventy-four (65.5%) studies used a before-and-after design, and sixteen (14.1%) were randomized trials. The majority (81.4%) described in-hospital ASPs with half of interventions in mixed pediatric wards and ten (8.8%) in emergency departments. Only sixteen (14.1%) studies focused on the costs of ASPs. Almost all the studies (79.6%) showed a significant reduction in inappropriate prescriptions. Compliance after ASP implementation increased. Sixteen of the included studies quantified cost savings related to the intervention with most of the decreases due to lower rates of drug administration. Seven studies showed an increased susceptibility of the bacteria analysed with a decrease in extended spectrum beta-lactamase producers E. coli and K. pneumoniae; a reduction in the rate of P. aeruginosa carbapenem resistance subsequent to an observed reduction in the rate of antimicrobial days of therapy; and, in two studies set in outpatient setting, an increase in erythromycin-sensitive S. pyogenes following a reduction in the use of macrolides.

Conclusions Pediatric ASPs have a significant impact on the reduction of targeted and empiric antibiotic use, healthcare costs, and antimicrobial resistance in both inpatient and outpatient settings. Pediatric ASPs are now widely implemented in the USA, but considerable further adaptation is required to facilitate their uptake in Europe, Asia, Latin America and Africa.

Authors: S. Rinaldi, V. Dinh, S. Pallikkuth, L. De Armas, R. Pahwa, N. Cotugno, E. Nastouli, C. Foster, P. Palma, S. Pahwa

Published in: Poster presented at 9^th International Workshop on HIV Persistence during Therapy; December, 2019; Miami, FL

Authors: Folgori L, Lutsar I, Standing JF, et al.

Published in: BMJ Open. 2019; 9:e032592

Authors: Blazquez-Gamero D, Soriano-Ramos M, Martinez de Aragon A, et al.

Published in: Pediatr Infect Dis J. 2019;38(11):1131-1137

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.

Authors: Turner B, Ford D, Moore C, Gibb D, Turkova A,  White I, and ODYSSEY trial team

Published in: Oral Presentation atInternational Society for Clinical Biostatics; July 16th 2019

Authors: Giovannetti M, de Mendonca MCL, Fonseca V, et al.

Published in: J Virol. 2019;94(1). pii: e01623-19

Abstract The recent reemergence of yellow fever virus (YFV) in Brazil has raised serious concerns due to the rapid dissemination of the virus in the southeastern region. To better understand YFV genetic diversity and dynamics during the recent outbreak in southeastern Brazil, we generated 18 complete and nearly complete genomes from the peak of the epidemic curve from nonhuman primates (NHPs) and human infected cases across the Espírito Santo and Rio de Janeiro states. Genomic sequencing of 18 YFV genomes revealed the estimated timing, source, and likely routes of yellow fever virus transmission and dispersion during one of the largest outbreaks ever registered in Brazil. We showed that during the recent epidemic, YFV was reintroduced from Minas Gerais to the Espírito Santo and Rio de Janeiro states multiple times between 2016 and 2019. The analysis of data from portable sequencing could identify the corridor of spread of YFV. These findings reinforce the idea that continued genomic surveillance strategies can provide information on virus genetic diversity and transmission dynamics that might assist in understanding arbovirus epidemics.

Authors: Goncalves BS, Nogueira RMR, Bispo de Filippis AM, Horta MAP

Published in: Trans R Soc Trop Med Hyg. 2019;113(11):670-677

Authors: Domínguez-Rodríguez S, Tagarro A. Palma P, et al.

Published in: JAIDS 2019;82(5):483-490

Authors: Schröter J.

Published in: Poster presented at 4th Workshop on Virus Dynamics, October 21st-23rd, 2019 -Paris, FR

Authors: Li G, Bielicki JA, Ahmed ASMNU, et al.

Published in: Arch Dis Child.2091;0:1-6

Authors:Simitsopoulou M, Kadiltzoglou P, Kyrpitzi D, Roilides E.

Published in: Int J Biol Med Res.2019;10(1):6591-6596