Publications

30

Nov, 2019

Modulated Zika virus NS1 conjugate offers advantages for accurate detection of Zika virus specific antibody in double antigen binding and Ig capture enzyme immunoassays

 

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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20

Nov, 2019

Universal Children’s Day

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Today, November 20th, is Universal Children’s Day. This year, we are celebrating in Cape Town, South Africa, where the EPIICAL 3rd General Assembly is being hosted. Universal Children’s Day is dedicated to the rights of the child, with one key aspect being the right for every child to access the highest standard of health. However, at the end of 2018, there were 37.9 million people living with HIV worldwide and, among them, 1.7 million are children aged less the 15 years.

The Early treated Perinatally HIV Infected Individuals (EPIICAL) is the world’s largest consortium dedicated to science of HIV remission, consisting of well-known scientists and clinicians working in HIV and pediatrics, from 26 institutions worldwide.

EPIICAL is strongly committed to fighting the HIV paediatric epidemic. Unique to the EPIICAL study are the cohorts of HIV-infected children who are treated early, and will be studied to develop strategies to develop treatment for HIV remission in HIV-infected children.
The knowledge gained from the consortium’s work has the potential to transform the lives of HIV-infected children worldwide, as well as potential applicability for the treatment of HIV in adults, particularly those who initiate early anti-retroviral therapy.

18

Nov, 2019

European Antibiotic Awareness Day

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Today, 18th of November, is European Antibiotic Awareness Day (EADD), that marks the start of the World Antibiotic Awareness Week (WAAW). WAAW aims to increase global awareness of antibiotic resistance, as well as  encourage best practices among the general public, health workers and policy makers to stop the spread of antibiotic resistance. The latest data from the European Centre for Disease Prevention and Control highlights that across the European Union, the number of patients infected by resistant bacteria is increasing. Emphasising the major threat antibiotic resistance continues to pose to public health. Infections caused by antibiotic resistant bacteria can be life-threatening, especially for those most vulnerable in society, such as children and especially newborns. However, until recently, the increasing trend in drug-resistant infections in infants and children has gone relatively unrecognized. In the last few years Penta has been involved in several European and global initiatives aimed at better characterising the use of antibiotics in children and infants, understanding the scale of resistance and investigating the best treatment regimens. At Penta, we are continuing to actively expand our activities in this important area and accelerate the development of treatments for infants and children. #KeepAntibioticsWorking #WakeUpToAMR

15

Nov, 2019

Penta’s Davide Bilardi wins award for outstanding research work

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The Graduate Studies Committee of the Nuffield Department of Medicine (NDM) at the University of Oxford (UK) assigns award prizes each year to current or recently graduated students of NDM supervisors. Prizes are awarded on the basis of student’s publication records, the impact and novelty of their research, and the impact of their research within and outside the department.

Davide Bilardi, Penta Project Manager and DPhil (PHD) student of NDM, has been awarded the “Outstanding work outside of degree” prize due to his ability to combine his academic career with his achievements outside the department and in society.

Congratulations Davide!

14

Nov, 2019

Analysing small groups within clinical trials, while borrowing information from larger groups

 

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

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14

Nov, 2019

Yellow Fever virus reemergence and spread in southeast Brazil, 2016-2019

 

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.

14

Nov, 2019

Factors predicting the severity of dengue in patients with warning signs in Rio de Janeiro, Brazil (1986–2012)

 

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

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

Background Since 1981, >12 million cases of dengue have been reported in Brazil. Early prediction of severe dengue with no warning signs is crucial to avoid progression to severe dengue. Here we aimed to identify early markers of dengue severity and characterize dengue infection in patients in Rio de Janeiro.
Methods We evaluated early severity markers, serotypes, infection status, number of days of illness and viral loads associated with dengue fever in patients from Rio de Janeiro, Brazil through an observational retrospective study (1986–2012). We compared dengue without warning signs and dengue with warning signs/severe dengue (DWWS/SD). Infection status was classified by enzyme-linked immunosorbent assay and viraemia was quantified by quantitative real-time reverse transcription polymerase chain reaction.
Results The presence of DWWS/ SD was significantly associated with younger age; patients 13–19 y of age had a significantly greater chance of presenting warning signs. Dengue virus type 3 (DENV3) was more likely to induce DWWS/SD, which was more frequent on days 4–5 of illness.
Conclusions DENV3, 4–5 d of illness and 13–19 y of age were early biomarkers of dengue severity. To our knowledge, this was the first study to analyse the characteristics of dengue severity in the state of Rio de Janeiro over 27 y of epidemics since the introduction of DENV.

14

Nov, 2019

EPIICAL data on Journal of AIDS: treat early, suppress fast!

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Treat early, suppress fast!

In a new paper just published online in Journal of AIDS, EPIICAL researchers investigated the association between the timing of antiretroviral therapy (ART) initiation and time-to suppression​ among HIV-infected infants who initiated​ ART within the first 28 days of life.

The study showed as children treated within 7 days of life have a faster​ time to viral suppression, which may result in a favorable ​impact on the viral reservoir.

These data strongly support the potential benefits of starting ART within 7 days of birth even in comparison to​ starting from 8 to 28 days after birth.

 

14

Nov, 2019

Reduced time to suppression among neonates with HIV initiating antiretroviral therapy within 7 days of age

 

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

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

Abstract There are limited data on infants with HIV starting antiretroviral therapy (ART) in the neonatal period. We investigated the association between the timing of ART initiation and time-to-suppression among infants who tested HIV-positive and initiated ART within the first 28 days of life. The effect was estimated using cumulative probability flexible parametric spline models and a multivariable generalized additive mixed model was performed to test nonlinear associations. Forty-four neonates were included. Nineteen (43.2%) initiated ART within 7 days of life and 25 (56.8%) from 8 to 28 days. Infants treated within 7 days were 4-fold more likely to suppress earlier than those treated after 7 days [Hazard ratio (HR) 4.01 (1.7–9.5)]. For each week the ART initiation was delayed, the probability of suppression decreased by 35% (HR 0.65 [0.46–0.92]). Age at ART start was linearly associated with time-to-suppression. However, a linear association with normally distributed residuals was not found between baseline viral load and time-to-suppression, with no association found when baseline viral loads were ≤5 log(10) copies/mL, but with exponential increase in time-to-suppression with > log5 copies/mL at baseline. Starting ART within 7 days of life led to 4-fold faster time to viral suppression, in comparison to initiation from 8 to 28 days.

12

Nov, 2019

Time to HIV suppression in perinatally infected infants depends on the viral load and CD4 T-cell percentage at the start of treatment

 

Authors: Schröter J.

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

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