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Displaying One Session

Session Type
PARALLEL SESSION
Date
Fri, 28.05.2021
Session Time
12:00 - 13:30
Room
Hall 02
Session Icon
Pre-Recorded with Live Q&A

EVALUATION OF THE PERFORMANCE OF A DENGUE IGG RAPID DIAGNOSTIC TEST FOR THE DETERMINATION OF DENGUE SEROSTATUS AS PART OF PRE-VACCINATION SCREENING (ID 907)

Abstract

Background

To determine the eligibility of receiving the tetravalent CYD-TDV dengue vaccine, indicated only in previously dengue virus (DV)-infected individuals, a highly specific and sensitive, point-of-care (POC) test is necessary. The clinical performance of the OnSiteTM Dengue IgG Rapid Diagnostic Test (RDT), a new lateral flow immunoassay specifically designed to determine prior DV infection status, was evaluated.

Methods

Archived pre-vaccination sera from 6-16 year-old participants of phase III trials in Asia (NCT01373281) and Latin America (NCT01374516) who consented to future research use were used. DV reference serostatus was determined by dengue PRNT90, PRNT50 and anti-NS1 IgG ELISA. Samples from seropositives with PRNT90 titer≥10 to only 1 serotype were subclassified as DV monotypic immune. Sensitivity was estimated using a random subset of DV seropositives (n=233); specificity using all available seronegative samples (n=346). Flavivirus (FV) cross-reactivity was assessed in DV seronegative samples with prior FV exposure documented by neutralization test, IgG ELISA, or known prior vaccination.

Results

The RDT displayed a specificity of 98.0% (95%CI: 95.9, 99.2) and a sensitivity of 95.3% (95%CI: 91.7, 97.6) in identifying prior DV infection status. Exploratory analysis showed 88.1% (52/59) sensitivity among DV monotypic immune samples. No RDT cross-reactivity was observed with samples positive for prior Zika (0/35) and WNV (0/32), with nominal cross-reactivity to YF (2.4%; 1/42) and JEV (2.8%; 1/36).

Conclusions

The OnSite™ Dengue IgG RDT was highly specific and sensitive in determining prior dengue infection status with minimal to no FV cross-reactivity. These findings support the use of this first-in-class POC test to determine dengue serostatus and eligibility to CYD-TDV vaccination.

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PARASITES UNDER THE RADAR: ASYMPTOMATIC INFECTION WITH PLASMODIUM FALCIPARUM ELICITS NO TRANSCRIPTOMIC HOST-RESPONSE (ID 174)

Abstract

Background

Naturally acquired immunity to malaria, which follows many previous infections, eventually allows individuals in endemic countries to tolerate infection without symptoms. However, asymptomatic infections do act as an undetected reservoir sustaining malaria transmission. Therefore, understanding the mechanisms enabling the asymptomatic state, and identifying biomarkers of asymptomatic infection could contribute to malaria elimination. This study analysed whole blood transcriptomes of Ghanaian children without malaria, with asymptomatic Plasmodium falciparum infection, and with symptomatic P. falciparum malaria to investigate the host response.

Methods

Children (n=37) were recruited in Obom, a high transmission peri-urban region in Ghana, frequency-matched for age and sex between groups. Illumina RNA-sequencing was undertaken from Paxgene whole blood samples. Differential gene expression analysis was conducted using DESeq2, with adjustment for variation in major leukocyte populations measured by flow-cytometry analysis (false discovery rate ≤ 5%).

Results

Comparison of symptomatic (n=9) vs uninfected (n=7) children revealed 735 differentially expressed genes, enriched in immune response pathways. In contrast, comparison of asymptomatic (n=21) vs uninfected (n=7) children showed no differentially expressed genes. We replicated these results by reanalysis of a published microarray dataset (Gene Expression Omnibus database ID: GSE1124).

Conclusions

These findings suggest that the asymptomatic state in P. falciparum infection is not the result of a suppressive response acting on-, or orchestrated by circulating blood cells. Parasites instead appear to be “under the radar”, not triggering any immune response at all. This suggests that host-response biomarkers of asymptomatic infection will not be successful and alternative mechanisms enabling and maintaining the asymptomatic state, including epigenetic modifications, should be investigated.

Clinical Trial Registration

My trial/study does not report the results of a controlled trial.

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MALARIA ANTIGEN SHEDDING IN BREASTMILK OF MOTHERS FROM A REGION WITH ENDEMIC MALARIA (ID 589)

Abstract

Background

More than 200 million cases of malaria occur yearly, with children under 5 years accounting for two thirds of all malaria deaths. Foreign antigens in breastmilk can elicit strong immune responses in breastfed offspring. We propose that malaria antigens in breastmilk may stimulate antimalarial immune defences. As a first step to address this, we investigated whether Plasmodium falciparum histidine-rich protein 2 (pHRP-2) and lactate dehydrogenase (pLDH) are detectable in breastmilk.

Methods

Asymptomatic malaria was diagnosed in blood of lactating Ugandan mothers (n=324) without clinical signs of malaria by an ultrasensitive pHRP-2-based rapid diagnostic test. The presence of malaria antigens in breastmilk was investigated by pHRP-2 and pLDH ELISA.

Results

Eighty-eight mothers (27%) harboured asymptomatic malaria. Among the breastmilk samples from these mothers, 7 had detectable pHRP-2 (7.9 %) with a median (interquartile range) level of 45.0 (2.0 pg/ml-180.2) pg/ml and 10 had detectable pLDH (11.3 %; 6.6 (5.6 AU/ml-9.9) AU/ml). Overall, 14 samples (15.9%) were positive for either pLDH or pHRP-2 and 3 (3.4%) were positive for both pLDH and pHRP-2. Forty-four milk samples from malaria-negative mothers were used as controls and none of these showed detectable pHRP-2 or pLDH antigens. Our preliminary data also indicated that blood levels of malaria antigens determine their levels in breastmilk.

Conclusions

This study shows for the first time that 15% of breastmilk samples from mothers with asymptomatic malaria contain malaria antigens. This may have important implications for child susceptibility to malaria, since malaria antigens in breastmilk may strongly influence the immune response in children who are breastfed.

Clinical Trial Registration

Clinical trial registration: N/A

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