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Displaying One Session

Session Type
PARALLEL SESSION
Date
Wed, 26.05.2021
Session Time
10:00 - 11:30
Room
Hall 03
Session Icon
Pre-Recorded with Live Q&A

ELEVATED LIPOPROTEIN(A) LEVELS IN EFFECTIVELY TREATED PERINATALLY HIV-INFECTED CHILDREN AND ADOLESCENTS OVER TIME (ID 491)

Lecture Time
10:00 - 10:07
Room
Hall 03

Abstract

Background

The incidence of cardiovascular disease (CVD) is higher in people living with HIV compared to the general population. Perinatally HIV-infected (PHIV+) children potentially have a greater CVD risk at older age, as their life expectancy normalized due to effective therapy. Lipoprotein(a) (Lp(a)) is an independent risk factor for CVD. We reported on higher Lp(a) levels in PHIV+ children compared to healthy matched controls in a previous cross-sectional study. To gain further insight in Lp(a) level trends and thus the potential CVD risk for PHIV+ children, we determined Lp(a) levels over time.

Methods

We determined Lp(a) levels of PHIV+ children from the Amsterdam UMC in the Netherlands on at least two occasions between September 2012 and September 2020, using the Architect c8000 Abbott (Lake Forest, IL, USA) with a reference value of < 300 mg/L. We assessed intra- and interindividual trends of Lp(a) and its determinants using mixed models.

Results

We included 36 PHIV+ children – of which 24 (67%) boys – with a median age (interquartile range) of 8.0 years (5.7-10.8) and a median Lp(a) level of 391 mg/L (IQR: 194-774). We found a positive association between Lp(a) and BMI, total cholesterol, low density lipoprotein and non-nucleoside reverse-transcriptase inhibitors (NNRTI). The intra-individual variability of Lp(a) was 33% (95%CI: 30-35).

Conclusions

We found importantly elevated and highly fluctuating Lp(a) levels over a period of eight years in PHIV+ children suggesting a higher CVD risk. The association between Lp(a) and NNRTI suggests it would be of interest to assess Lp(a) levels when switching therapy. Studies investigating CVD risk for PHIV+ children at older age could lead to strategies reducing their CVD risk including the development of therapies lowering Lp(a) levels.

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ASSESSMENT OF SPECIFIC IMMUNOLOGICAL RESPONSE AFTER ADMINISTRATION OF ANTI-MENINGOCOCCAL QUADRIVALENT CONJUGATE VACCINE MENVEO® IN A POPULATION WITH VERTICALLY-TRANSMITTED HIV INFECTION (ID 770)

Lecture Time
10:07 - 10:14
Room
Hall 03

Abstract

Background

In HIV-infected patients, high incidence of invasive meningococcal disease is reported. Moreover, HIV subjects, because of immune abnormalities, may undergo impaired vaccine response. Our study aims to assess the immune response after a booster dose of quadrivalent meningococcal conjugate vaccine Menveo® (MenACWY-CRM, GlaxoSmithKline Vaccines) in HIV-infected youth.

Methods

We carried out a controlled, non-randomized, observational and prospected study, involving 27 HIV-infected patients aged 9–30 years, reporting vertically-transmitted HIV infection and followed at the Paediatric Infectious Disease Unit of ASST FBF-Sacco, Milan, Italy. All patients enrolled were on HAART, and 25 out of 27 presented optimal immunological and viral response. Each subject received a booster dose of vaccine Menveo® (0,5 ml i.m.). MenACWY-specific Ab titer, viral load and CD4+ T cells count were measured at baseline (T0), T3, T6 and T12 months post vaccination. In 14 patients, MenACWY-specific cell-mediated immune responses were evaluated at the same time points.

Results

The booster dose induced seroconversion in all subjects except one. We divided our cohort in different subgroups: Responders (R), reporting seroconversion at T3, Highly-Responders (HR) with a high Ab titer at T0, and Non-Responders (NR). The booster dose induced MenACWY-specific cell-mediated immunity at T12 mainly in HRs (Effector Memory CD4+T cells). MenACWY-specific IL2-secreting CD4+ and CD8+ T cells were slightly increased in both HRs and Rs. In the NR group, terminally-differentiated CD4+ and CD8+ T cells were the only parameters modified at all time points.

Conclusions

The booster dose of Menveo® vaccine, considering both R and HR subgroups, induced a valid antibody-mediated protection. Moreover, we observed the development of a stable T cell-mediated immune memory that lasted robustly up to one year since vaccination. Alternate immunization schedules need to be considered in NR.

Clinical Trial Registration

Not applicable

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BRAIN MRI AND NEUROCOGNITIVE CHARACTERISTICS OF CHILDREN WITH PERINATAL HIV INFECTION IN RUSSIA: A CROSS-SECTIONAL STUDY. (ID 1277)

Lecture Time
10:14 - 10:21
Room
Hall 03

Abstract

Background

Russia has the largest HIV epidemic in the Eastern Europe and Central Asia (EECA) region. This study describes the neurocognitive and neuroradiological characteristics of children and adolescents with perinatal HIV (CAPHIV) attending a tertiary paediatric HIV clinic in Russia.

Methods

A cross-sectional pilot study was conducted in the Republican Hospital for Infectious Diseases (RHID) in Saint Petersburgh from September 2013 to July 2015. 39 consecutive children/carers in routine follow up were approached to undergo MRI imaging (1.5 T MRI with T1-weighted, T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequences) and cognitive function assessment using the Russian version of the Weschler Intelligence Scale for Children (WISC-III). The average range was defined as 90 to 110 for IQ indexes (verbal, performance and full-scale) and 8 to 12 for cognitive subtest scores.

Results

32 children completed the study (56.3% were female, median age[IQR] at HIV diagnosis 21.5[8.5-35.5]months, age at ART start 5.9[2.3-7.8]years). At study entry, median age was 10[8-11.75]years, all were on protease inhibitor-based ART, CDC immunological category was 1 in 18(56.3%) children, 2 in 4(12.5%) and 3 in 10(31.3%).

Nine(28.1%) participants had ≥1 focal supratentorial white matter (WM) lesions, 4(12.5%) diffuse WM hyperdensity lesions on T2/FLAIR, 5(15.6%) mild global atrophy.

Mean(SD) WISC-III IQ and subtests scores were within the average range on all but two subtests: vocabulary 7(5.1) and digit-span 7.9(2.5).

Conclusions

Over a quarter of children had neuroradiological abnormalities but most had IQ scores within the average range except for few subtests scores. These assessments may help identify children in need of development support and ART optimisation.

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SCAR FORMATION FOLLOWING INFANT IMMUNISATION WITH BACILLE CALMETTE-GUÉRIN IS ASSOCIATED WITH ENHANCED MYCOBACTERIUM-SPECIFIC T-CELL RESPONSES (ID 72)

Lecture Time
10:21 - 10:28
Room
Hall 03

Abstract

Background

Limited evidence suggests that scar formation after bacille Calmette-Guérin (BCG) immunisation is associated with lower all-cause mortality but does not correlate with protection against tuberculosis. The aim of this post-hoc analysis was to evaluate the association between BCG scar characteristics and the mycobacterial-specific immune response.

Methods

208 infants in Australia were randomised to receive one of three BCG vaccine strains at birth (BCG-Denmark, n=53; BCG-Japan, n=55; or BCG-Russia, n=56) or at 2 months of age (BCG-Denmark, n=44). The size and characteristics of BCG scars were assessed 10 weeks after immunisation. At the same time point, intracellular cytokine secretion (IFNg, IL-2 and TNF) in whole blood assays following in-vitro stimulation with M. tuberculosis, M. ulcerans, PPD and BCG was determined using multi-colour flow cytometry. The relationship between BCG scar characteristics and immunological responses was analysed.

Results

Proportions of single, double, and triple antigen-specific cytokine-producing CD4+ T-cells were significantly higher in children who developed a BCG scar compared to those without a scar. The magnitude of the immune response correlated with the size and characteristic of the BCG scar (Figure), even after adjusting for BCG vaccine strain and timing of immunisation in a mixed model analysis.

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Conclusions

BCG scar formation is associated with higher mycobacteria-specific T-cell responses. As T-cell responses are important in the immune response against TB, the relationship between BCG scar formation and protection against TB should be explored further.

Clinical Trial Registration

Australian clinical trials registration number: ACTRN12608000227392

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GETTING THE DIAGNOSIS RIGHT IN CHILDHOOD TB: FIRST RESULTS ON NEW TEST PERFORMANCES FROM “RAPAED-TB” (ID 952)

Lecture Time
10:28 - 10:35
Room
Hall 03

Abstract

Background

The diagnosis of tuberculosis (TB) in children remains challenging: current detection methods neither perform reliably nor are sampling methods child-friendly.

Methods

RaPaed-TB is a diagnostic validation study currently conducted in South Africa, Mozambique, Malawi, Tanzania, and India. Enrolment of children ≤14years was initiated in 01/2019. Clinical and laboratory workup is standardized across sites, and diagnostic classification follows the current NIH-consensus statement. New tests conducted on site include: blood-based T-cell activation-marker for TB (TAM-TB); urine-based lateral-flow assay Fuji SILVAMP-TB LAM (FujiLAM); and Stool Processing Kit (SPK) for MTB-DNA detection. Recruitment, data entry and analysis are underway; presented data are preliminary and totals differ dependent on data-entry status.

Results

As of mid-January 2021, 733 participants were enrolled. The median age was 4.8 years (IQR 1.8;8.8 years), with 14% of children being ≤1-year (100/701), and 52% <5years (361/701). Overall, 17% (115/694) are HIV -infected, while 15% (107/694) were HIV-exposed uninfected. Microbiological confirmation rate (PCR/culture) was 24% (178/733). New tests conducted on site include TAM-TB, with a sensitivity of 56% and specificity of 91%. FujiLAM had a sensitivity of 42% and a specificity of 86%, while SPK was 40% sensitive and 93% specific. Sensitivity of all tests was significantly improved when excluding children confirmed solely by “trace” results. Subgroup analysis showed promising performances in the children <1year.

Conclusions

The RaPaed-TB cohort allows large-scale evaluation of new tests. Presented data indicate a promising performance of TAM-TB, while FujiLAM and SPK alone had modest sensitivity. All three tests show promising performances in the very young and malnourished, showing their potential to aid diagnosis in these particularly vulnerable groups. Ongoing comprehensive new testing encompasses pathogen detection, host-immune response, biomarker-assays, and biobanking; further results to be presented.

Clinical Trial Registration

NCT03734172

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CHALLENGES IN PAEDIATRIC RADIOLOGICAL DIAGNOSIS OF PULMONARY TUBERCULOSIS FOLLOWING AN OUTBREAK IN A NURSERY SCHOOL (ID 855)

Lecture Time
10:35 - 10:42
Room
Hall 03

Abstract

Background

Tuberculosis (TB) outbreaks often occur among people who share a closed space for long periods, such as schools, nursing homes or hospitals. Chest radiography (CXR) is one of the cornerstones for evaluating TB outbreaks, but it has several limitations, especially in young infants. Computed tomography (CT) provides assessment in challenging cases. This study aimed to analyze CT´s contribution to paediatric TB diagnosis during an outbreak in a nursery school that involved children <6 years.

Methods

472 children evaluated during a TB outbreak underwent a Tuberculin Skin Test (TST). Children with positive TST and those presenting signs or symptoms suggestive of TB were referred to our tertiary hospital in Madrid, Spain. A CT scan was performed in children with doubtful findings on CXR, or with compatible symptomatology but normal CXR.

Results

figure 1.pngSeventy-eight patients were evaluated at hospital [median age 5.1 years (IQR: 3.7-5.5)]; 37.2% were girls. Of the 78 CXR performed, 32 (41.0%) showed no abnormalities, 14 (17.9%) were inconclusive, and 32 (41.0%) compatible with pulmonary TB. Among 33 children with inconclusive diagnosis after CXR, CT helped rule out TB in 14 patients (42.4%), and confirm TB in 19 (57.6%) (Figure 1). The final diagnosis was pulmonary TB in 35 cases (8 microbiologically confirmed TB and 27 probable TB), latent TB in 24 (30.8%), and non-TB in 19 (24.4%).

Conclusions

In this study, 7.4% of the 472 exposed children to an outbreak were diagnosed of pulmonary TB. CXR was unable to detect early TB-related radiological abnormalities in approximately half of the patients. CT can detect pathological findings not seen on CXR, and is useful in helping to decide on antibiotic treatment.

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NEONATAL BCG VACCINATION REDUCES THE RISK OF ECZEMA IN PREDISPOSED INFANTS – RESULTS FROM THE MIS BAIR RANDOMISED CONTROLLED TRIAL (ID 148)

Lecture Time
10:42 - 10:49
Room
Hall 03

Abstract

Background

Bacille Calmette-Guérin (BCG) vaccine could play a role in counteracting the rising prevalence of atopic diseases through its beneficial off-target effects. One aim of the MIS BAIR trial was to determine whether neonatal BCG vaccination reduces the incidence of eczema in the first year of life.

Methods

In this randomised controlled trial, the incidence and severity of eczema in the first 12 months of life was determined with 3-monthly questionnaires using the UK diagnostic tool and POEM score, respectively. Eczema was also assessed at a 12-month clinic visit using SCORAD.

Results

1272 infants were randomised to receive BCG-Denmark (median 1.5 days of life; IQR 0.9 to 2.5) or no BCG. The incidence of eczema in the first 12 months of life was lower in the BCG group (32.2%) compared with controls (36.6%) (risk difference (RD) -4.3%,95%CI -9.9% to 1.3%; multiple imputation model), resulting in a number needed to treat (NNT) of 23. Compared with controls, infants in the BCG group were less likely to have active eczema lesions at the 12-month visit (15.7% vs.19.2%;RD -3.5%,95%CI -8.0% to 1.0%), to use topical steroids (35.7% vs.39.0%;RD -3.3%,95%CI -9.2 to 2.7), and to have severe eczema scores (7.3% vs.10.2%;RD -3.0%,95%CI -8.8% to 2.7%), especially in the 3-month questionnaire (4.9% vs.15.9%;RD -11.0%,95%CI -23.7% to 1.6%). In high-risk infants (two atopic parents, n=344), the incidence of eczema was lower in the BCG group (35.3%) compared with controls (46.8%) (RD -11.5%,95%CI -21.9% to -1.2%) with a NNT of 8.7 (95%CI 4.6 to 83.3).

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Conclusions

A single dose of BCG-Denmark soon after birth reduced the incidence of eczema, especially in infants with two atopic parents. There is insufficient evidence to recommend neonatal BCG vaccination for the general prevention of eczema.

Clinical Trial Registration

ClinicalTrial.gov: NCT01906853.

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DIAGNOSTIC PERFORMANCE OF A FIVE-MARKER TRANSCRIPTOMIC SIGNATURE FOR DIAGNOSIS OF CHILDHOOD TUBERCULOSIS IN AN AFRICAN MULTI-COUNTRY COHORT (ID 1700)

Lecture Time
10:49 - 10:56
Room
Hall 03

Abstract

Background

Each year approximately 1.2 million children develop active tuberculosis (TB) disease, with 230,000 deaths. Microbiological diagnosis of TB remains challenging. Gene expression signatures in blood may offer a non-sputum diagnostic test. However, gene expression signatures discovered in adult populations underperform in children, while the few paediatric studies focus discovery on specific countries. We undertook a multi-country gene expression signature discovery study, to identify an accurate signature for paediatric TB.

Methods

Whole blood was collected from 571 children (<15 years of age), 264 (48%) with microbiologically confirmed TB and 307 (52%) with other diseases (OD), presenting to hospitals in South Africa, Malawi, Kenya or The Gambia with suspected TB between 2008 and 2018. Cases included those with pulmonary or extra-pulmonary TB, with or without HIV-infection. RNA extraction and RNA-sequencing were done on blood samples collected at enrolment. Quality control, differential expression and feature selection analysis was conducted in R; data were batch-corrected and normalised.

Results

Differential expression analysis accounting for age and site identified 208 candidate biomarker genes. A feature selection algorithm with cross-validation (randomly selecting 80% of the data as training set and 20% as test set), run on the 208 genes, selected a 5-gene signature to distinguish TB from ODs with an AUC of 91.30%, sensitivity of 84.85% and a specificity of 83.06% when maximising the Youden index. When sensitivity was fixed at 72.00%, which is the minimum WHO requirement of a non-sputum test for TB in children, specificity was 92.51%, meeting the optimal WHO requirement for specificity.

Conclusions

A 5-gene transcriptomic signature met the minimum WHO Target Product Profile criteria for a non-sputum-based test for TB in children. Further cross-sample, cross-platform validation using targeted methods (i.e. RT-PCR) will follow.

Clinical Trial Registration

Not applicable

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PNEUMOCYSTIS - STILL AN OPPORTUNISTIC AGENT TO KEEP IN MIND (ID 1622)

Lecture Time
10:56 - 11:03
Room
Hall 03

Abstract

Background

Pneumocystis pneumonia (PCP) is a potentially life-threatening infection that occurs in immunocompromised individuals. HIV-infected patients with a low CD4 count are at the highest risk of PCP. Although the use of routine prophylaxis in HIV-infected patients led to reduced rates of PCP in that population, it remains a significant cause of pneumonia in patients with other types of immunodeficiencies, such as severe combined immunodeficiency (SCID).

The aim of this study is to characterize the patients with a diagnosis of PCP admitted in our paediatric unit at a tertiary hospital.

Methods

Retrospective, observational and descriptive study. Literature review and sample characterization by consulting the patients’ health records with descriptive statistical analysis of the data.

Results

Six PCP cases were reviewed, two HIV infected-patients with high viral load and four SCID patients. 75% diagnosed in the first 6 months of life. 75% of SCID cases were male. All but one required O2 supplementation, with two of the SCID patients needing mechanical ventilation for more than 1 week. All exhibited oral candidiasis and poor weight progression on admission. 50% hepatomegaly and/or BCGitis. All SCID patients had hypogammaglobulinemia and T-cell lymphopenia (average total lymphocyte count 1630 mm3, CD4+ 24 mm3 and CD8+ 4 mm3).

Conclusions

Pneumocystis remains a relevant opportunistic pathogen. It can present with insidious respiratory failure associated dry cough and progressive hypoxemia and is a life-threatening infection.

HIV infection should always be investigated. A defect in cell-mediated immunity, specially SCID, must be considered when a pneumonia has a radiographic pattern of diffuse, bilateral, interstitial infiltrates that does not respond to empiric therapy in non-HIV patients. Failure to thrive combined with recurrent oral candidiasis as well as lymphopenia and absent thymic shadow are other alarm signs.

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