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Seroconverting blood donors as a resource for characterising and optimising recent infection testing algorithms for incidence estimation.

Kassanjee R, Welte A, McWalter TA, Keating SM, Vermeulen M, Stramer SL, Busch MP - PLoS ONE (2011)

Bottom Line: Within an idealised model for the dynamics of false-recent results, blood donor specimens were used to characterise RITAs by a new method that maximises the likelihood of cohort-level recency classifications, rather than modelling individual sojourn times in recency.Assessment of the Vitros-LS (n = 108) suggested potentially high false-recent rates.The Vironostika-LS and Vitros-LS warrant further analysis to provide greater precision of estimates.

View Article: PubMed Central - PubMed

Affiliation: South African DST/NRF Centre for Epidemiological Modelling and Analysis, University of Stellenbosch, Stellenbosch, South Africa. r.kassanjee@gmail.com

ABSTRACT

Introduction: Biomarker-based cross-sectional incidence estimation requires a Recent Infection Testing Algorithm (RITA) with an adequately large mean recency duration, to achieve reasonable survey counts, and a low false-recent rate, to minimise exposure to further bias and imprecision. Estimating these characteristics requires specimens from individuals with well-known seroconversion dates or confirmed long-standing infection. Specimens with well-known seroconversion dates are typically rare and precious, presenting a bottleneck in the development of RITAs.

Methods: The mean recency duration and a 'false-recent rate' are estimated from data on seroconverting blood donors. Within an idealised model for the dynamics of false-recent results, blood donor specimens were used to characterise RITAs by a new method that maximises the likelihood of cohort-level recency classifications, rather than modelling individual sojourn times in recency.

Results: For a range of assumptions about the false-recent results (0% to 20% of biomarker response curves failing to reach the threshold distinguishing test-recent and test-non-recent infection), the mean recency duration of the Vironostika-LS ranged from 154 (95% CI: 96-231) to 274 (95% CI: 234-313) days in the South African donor population (n = 282), and from 145 (95% CI: 67-226) to 252 (95% CI: 194-308) days in the American donor population (n = 106). The significance of gender and clade on performance was rejected (p-value = 10%), and utility in incidence estimation appeared comparable to that of a BED-like RITA. Assessment of the Vitros-LS (n = 108) suggested potentially high false-recent rates.

Discussion: The new method facilitates RITA characterisation using widely available specimens that were previously overlooked, at the cost of possible artefacts. While accuracy and precision are insufficient to provide estimates suitable for incidence surveillance, a low-cost approach for preliminary assessments of new RITAs has been demonstrated. The Vironostika-LS and Vitros-LS warrant further analysis to provide greater precision of estimates.

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Related in: MedlinePlus

Comparison of mean recency duration estimates for the Vironostika-LS to previously published estimates.Estimates of the mean recency duration, ω, under both the simultaneous estimation of ω and α, and when assuming α = 0%, for T = 1 year, are compared to published estimates (by ‘back-calculation’ in the repeat donor population [27] and using seroconversion panels [18], [27]) as a function of test threshold. The minimum and maximum ω occurring in the 95% confidence regions (CRs) for ω and α (simultaneous estimation), as well as 95% confidence interval (CI) limits for ω (assuming α = 0%, with no uncertainty) are also displayed. Estimates shown in Part A pertain to the South African population, while those in Part B pertain to the USA population.
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pone-0020027-g002: Comparison of mean recency duration estimates for the Vironostika-LS to previously published estimates.Estimates of the mean recency duration, ω, under both the simultaneous estimation of ω and α, and when assuming α = 0%, for T = 1 year, are compared to published estimates (by ‘back-calculation’ in the repeat donor population [27] and using seroconversion panels [18], [27]) as a function of test threshold. The minimum and maximum ω occurring in the 95% confidence regions (CRs) for ω and α (simultaneous estimation), as well as 95% confidence interval (CI) limits for ω (assuming α = 0%, with no uncertainty) are also displayed. Estimates shown in Part A pertain to the South African population, while those in Part B pertain to the USA population.

Mentions: The estimated mean recency durations, for a number of thresholds (holding T at 1 year), are compared to published estimates (Fig. 2):


Seroconverting blood donors as a resource for characterising and optimising recent infection testing algorithms for incidence estimation.

Kassanjee R, Welte A, McWalter TA, Keating SM, Vermeulen M, Stramer SL, Busch MP - PLoS ONE (2011)

Comparison of mean recency duration estimates for the Vironostika-LS to previously published estimates.Estimates of the mean recency duration, ω, under both the simultaneous estimation of ω and α, and when assuming α = 0%, for T = 1 year, are compared to published estimates (by ‘back-calculation’ in the repeat donor population [27] and using seroconversion panels [18], [27]) as a function of test threshold. The minimum and maximum ω occurring in the 95% confidence regions (CRs) for ω and α (simultaneous estimation), as well as 95% confidence interval (CI) limits for ω (assuming α = 0%, with no uncertainty) are also displayed. Estimates shown in Part A pertain to the South African population, while those in Part B pertain to the USA population.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3111407&req=5

pone-0020027-g002: Comparison of mean recency duration estimates for the Vironostika-LS to previously published estimates.Estimates of the mean recency duration, ω, under both the simultaneous estimation of ω and α, and when assuming α = 0%, for T = 1 year, are compared to published estimates (by ‘back-calculation’ in the repeat donor population [27] and using seroconversion panels [18], [27]) as a function of test threshold. The minimum and maximum ω occurring in the 95% confidence regions (CRs) for ω and α (simultaneous estimation), as well as 95% confidence interval (CI) limits for ω (assuming α = 0%, with no uncertainty) are also displayed. Estimates shown in Part A pertain to the South African population, while those in Part B pertain to the USA population.
Mentions: The estimated mean recency durations, for a number of thresholds (holding T at 1 year), are compared to published estimates (Fig. 2):

Bottom Line: Within an idealised model for the dynamics of false-recent results, blood donor specimens were used to characterise RITAs by a new method that maximises the likelihood of cohort-level recency classifications, rather than modelling individual sojourn times in recency.Assessment of the Vitros-LS (n = 108) suggested potentially high false-recent rates.The Vironostika-LS and Vitros-LS warrant further analysis to provide greater precision of estimates.

View Article: PubMed Central - PubMed

Affiliation: South African DST/NRF Centre for Epidemiological Modelling and Analysis, University of Stellenbosch, Stellenbosch, South Africa. r.kassanjee@gmail.com

ABSTRACT

Introduction: Biomarker-based cross-sectional incidence estimation requires a Recent Infection Testing Algorithm (RITA) with an adequately large mean recency duration, to achieve reasonable survey counts, and a low false-recent rate, to minimise exposure to further bias and imprecision. Estimating these characteristics requires specimens from individuals with well-known seroconversion dates or confirmed long-standing infection. Specimens with well-known seroconversion dates are typically rare and precious, presenting a bottleneck in the development of RITAs.

Methods: The mean recency duration and a 'false-recent rate' are estimated from data on seroconverting blood donors. Within an idealised model for the dynamics of false-recent results, blood donor specimens were used to characterise RITAs by a new method that maximises the likelihood of cohort-level recency classifications, rather than modelling individual sojourn times in recency.

Results: For a range of assumptions about the false-recent results (0% to 20% of biomarker response curves failing to reach the threshold distinguishing test-recent and test-non-recent infection), the mean recency duration of the Vironostika-LS ranged from 154 (95% CI: 96-231) to 274 (95% CI: 234-313) days in the South African donor population (n = 282), and from 145 (95% CI: 67-226) to 252 (95% CI: 194-308) days in the American donor population (n = 106). The significance of gender and clade on performance was rejected (p-value = 10%), and utility in incidence estimation appeared comparable to that of a BED-like RITA. Assessment of the Vitros-LS (n = 108) suggested potentially high false-recent rates.

Discussion: The new method facilitates RITA characterisation using widely available specimens that were previously overlooked, at the cost of possible artefacts. While accuracy and precision are insufficient to provide estimates suitable for incidence surveillance, a low-cost approach for preliminary assessments of new RITAs has been demonstrated. The Vironostika-LS and Vitros-LS warrant further analysis to provide greater precision of estimates.

Show MeSH
Related in: MedlinePlus