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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

Estimated RITA characteristics for the Vitros-LS in the South African repeat donor population.The estimates of the RITA characteristics, ω and α, under the simultaneous estimation of the parameters are provided, as a function of the cutoff time T, for T = 1 year to T = 2.5 years. In Part A and Part B, estimates of ω and α are plotted, respectively. The minimum and maximum ω and α occurring in the 95% confidence regions (CRs) for these parameters are also displayed. *A polynomial is fitted by least squares to smooth estimates.
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pone-0020027-g005: Estimated RITA characteristics for the Vitros-LS in the South African repeat donor population.The estimates of the RITA characteristics, ω and α, under the simultaneous estimation of the parameters are provided, as a function of the cutoff time T, for T = 1 year to T = 2.5 years. In Part A and Part B, estimates of ω and α are plotted, respectively. The minimum and maximum ω and α occurring in the 95% confidence regions (CRs) for these parameters are also displayed. *A polynomial is fitted by least squares to smooth estimates.

Mentions: Preliminary RITA characteristic estimates of the currently used Vitros-LS (using a threshold of 20), for the South African repeat donor population, are shown (Fig. 5). The simultaneous estimation of ω and α, for a range of T, was performed (n = 108 for T = 1 year reduces to n = 59 for T = 2.5 years). Observed and expected percentages of seroconverters who were recently infected were also compared (SDC S1, Section E).


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)

Estimated RITA characteristics for the Vitros-LS in the South African repeat donor population.The estimates of the RITA characteristics, ω and α, under the simultaneous estimation of the parameters are provided, as a function of the cutoff time T, for T = 1 year to T = 2.5 years. In Part A and Part B, estimates of ω and α are plotted, respectively. The minimum and maximum ω and α occurring in the 95% confidence regions (CRs) for these parameters are also displayed. *A polynomial is fitted by least squares to smooth estimates.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0020027-g005: Estimated RITA characteristics for the Vitros-LS in the South African repeat donor population.The estimates of the RITA characteristics, ω and α, under the simultaneous estimation of the parameters are provided, as a function of the cutoff time T, for T = 1 year to T = 2.5 years. In Part A and Part B, estimates of ω and α are plotted, respectively. The minimum and maximum ω and α occurring in the 95% confidence regions (CRs) for these parameters are also displayed. *A polynomial is fitted by least squares to smooth estimates.
Mentions: Preliminary RITA characteristic estimates of the currently used Vitros-LS (using a threshold of 20), for the South African repeat donor population, are shown (Fig. 5). The simultaneous estimation of ω and α, for a range of T, was performed (n = 108 for T = 1 year reduces to n = 59 for T = 2.5 years). Observed and expected percentages of seroconverters who were recently infected were also compared (SDC S1, Section E).

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