Thesis defense Roy Zuurbier

Thursday, June 1, 2023 at 2:15 PM - Thursday, June 1, 2023 at 3:15 PM
Thesis defense Roy Zuurbier

All promotions can be followed live via this link

In this thesis I have described the use of different point-of-care tests (POCTs) on respiratory syncytial virus (RSV) as well as the burden and dynamics of respiratory viruses in infants⁠. I will first summarise the main findings of this thesis after which I will discuss clinical implications and future perspectives of part one on RSV point-of-care testing⁠.

1⁠. Part one: RSV point-of-care testing
In part one of the thesis I described the use of different POCTs on RSV in infants and in older adults⁠. In recent years, several POCTs have been developed to detect RSV⁠. Our studies were performed within our international RESCEU birth cohort and older adult cohort in which the primary objective was to determine the burden of RSV⁠. Because of the prospective character of these cohort studies we were able to examine the accuracy of different rapid tests in a community setting, with different levels of severity of RSV infections⁠.

In Chapter 2 the performance of rapid antigen detection test BinaxNOW® RSV (BN) was evaluated⁠. Samples of infants with acute respiratory tract infections (ARTIs) with different degrees of disease severity were analysed with BN compared to molecular diagnosis⁠. In total, 162 respiratory samples from 148 children were studied⁠. Low sensitivity was found of rapid antigen test BN for RSV detection in infants, with a sensitivity of 7⁠.6% (95% CI 3⁠.3-16⁠.5%), specificity was 100% (95% CI 96⁠.2-100%)⁠. Sensitivity was slightly higher in the subgroup of infants admitted to a PICU compared to less severe ill infants (22⁠.2% versus 5⁠.3%), although this difference was not statistically significant (p=0⁠.134) and sensitivity remained low⁠.

The performance of a molecular rapid detection test in older adults was assessed in Chapter 3⁠. Respiratory samples of participants of RESCEU’s older cohort study were collected each time they experienced an ARTI⁠. Performance of the Xpert® Xpress Flu⁠/RSV assay was evaluated to diagnose RSV infection in home-dwelling older adults (≥60 years) with ARTI in different clinical settings⁠. The performance of Xpert® Xpress Flu⁠/RSV compared to routine RT-PCR is high for RSV detection in home-dwelling older adults⁠. In all cases with discordant results for the two assays, viral load was low⁠. The positive percentage agreement (PPA) was 90⁠.9% (95% CI 76⁠.4-96⁠.8%) and negative percentage agreement (NPA) was 99⁠.7% (95% CI 99⁠.0-99⁠.9%)⁠. PPA was used as outcome, rather than sensitivity, to show agreement between two accurate tests⁠. The assay is fast and easy to use and therefore has the ability to improve patient management and outcomes⁠.

2⁠. Part two: respiratory viruses in infants
In part two of this thesis I discussed the burden and dynamics of respiratory viruses in infants⁠. Results are based on a hospital based cohort and two different birth cohort studies: the Dutch MUIS birth cohort study and the international RESCEU infant cohort study⁠. Both birth cohort studies, MUIS and the Dutch part of RESCEU, were performed at a general hospital, Spaarne Gasthuis in the northern part of the Netherlands⁠. Within these cohorts we were able to investigate different degrees of severity⁠.

In Chapter 4 we examined the occurrence of respiratory viruses in infants during the first year of life⁠. 1,304 nasopharyngeal samples were obtained from 11 consecutive regular sampling moments and during an ARTI⁠. Rhinovirus (RV) was negatively associated with ARTI (aOR 0⁠.41 [95% CI 0⁠.18-0⁠.92])⁠. Human metapneumovirus, RSV, parainfluenza (PIV) 2 and 4, and human coronavirus (HCoV) HKU1 were positively associated with ARTI⁠. Asymptomatic RV in early life was, however, associated with increased susceptibility to and recurrence of ARTIs later in the first year of life (Kaplan-Meier survival analysis: p=0⁠.022)⁠. Overall, respiratory viruses are often detected in infants and are often asymptomatic⁠.

The methods of the prospective international RESCEU birth cohort study was described in Chapter 5⁠. This multicenter study had the aim to recruit 10,000 healthy term infants during 3 consecutive years, including a nested cohort of 1,000 infants who were followed actively⁠. In this nested cohort, during all ARTIs in the RSV season, a respiratory swab was collected for RSV molecular diagnosis⁠. The primary outcome was the incidence of RSV associated ARTI, medically attended (MA)-ARTI, and hospitalisation in the first year of life⁠. This will provide key information to fill the gaps in knowledge about the burden of RSV disease in healthy term infants and support decision making for implementation of new prevention strategies⁠.

The results of this study were shown in Chapter 6⁠. In total 9,154 infants born between July 2017 and April 2020 were followed during the first year of life of whom  993 participated in the nested active surveillance⁠. The incidence of RSV hospitalisation in the total cohort was 1⁠.8% (95% CI 1⁠.6-2⁠.1)⁠. About half of hospitalisations for respiratory tract infection in the first year of life were associated with RSV⁠. The majority (57⁠.9%) of RSV hospitalizations occurred in children <3 months of age⁠. Incidences of RSV infection and medically-attended RSV infection in the active surveillance cohort were 26⁠.2% (95% CI 24⁠.0-28⁠.6) and 14⁠.1% (95% CI 12⁠.3-16⁠.0), respectively⁠. Immunisation of pregnant women or healthy term-born infants during their first winter season could have a significant impact on the healthcare burden caused by RSV infections⁠.

The burden of influenza and RSV in infants of the Dutch part of RESCEU was discussed in Chapter 7⁠. An overall incidence of  3⁠.2% (6⁠/187) for influenza-ARTI and 35⁠.8% (67⁠/187) for RSV-ARTI was found in the birth cohort⁠. The hospital cohort was performed in a general hospital, Spaarne Gasthuis⁠. In this cohort, influenza was detected in 7⁠.6% (23⁠/304) of hospitalised infants with an ARTI, for RSV this was 49⁠.3% (150⁠/304)⁠. RSV was responsible for the highest number of ARTIs in both non-hospitalised and hospitalised infants, especially during the first months of life⁠. Incidence of influenza-ARTI was low compared to RSV-ARTI⁠. These findings suggest most emphasis should be on RSV prevention strategies, especially in the first months of life⁠.