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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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Estimated RITA characteristics for the Vironostika-LS in the repeat donor population.The estimates of the mean recency duration, ω, under both the simultaneous estimation of ω and α, and when using an input α, for T = 1 year, are provided. For the latter estimation, the estimated ω is plotted as a function of the assumed α. The 95% confidence regions (CRs) for ω and α (simultaneous estimation) and confidence intervals (CIs) for ω (assuming α, and not accounting for uncertainty in α) are displayed. Part A shows the results for the South African repeat donor sample, while Part B shows the results for the USA repeat donor sample.
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pone-0020027-g001: Estimated RITA characteristics for the Vironostika-LS in the repeat donor population.The estimates of the mean recency duration, ω, under both the simultaneous estimation of ω and α, and when using an input α, for T = 1 year, are provided. For the latter estimation, the estimated ω is plotted as a function of the assumed α. The 95% confidence regions (CRs) for ω and α (simultaneous estimation) and confidence intervals (CIs) for ω (assuming α, and not accounting for uncertainty in α) are displayed. Part A shows the results for the South African repeat donor sample, while Part B shows the results for the USA repeat donor sample.

Mentions: The estimated RITA characteristics (using a threshold of 1) are shown (Fig. 1), for both estimation assuming a known α, and simultaneous estimation of ω and α. Observations with Δi>T = 1 year were used (the maximum duration in the state of recency has been estimated to be 200 days [26] and 1 year [17]), resulting in sample sizes of n = 282 and n = 106 for the South African and American datasets respectively. A comparison of the observed percentages of seroconverters who were recently infected to the expected percentages (by substituting the estimated RITA characteristics into (8)), as functions of ID interval, suggests good agreement under simultaneous estimation of the RITA characteristics (SDC S1, Section C). When exploring the sensitivity of results to T, when T was increased to 2.5 years, estimates from the South African dataset varied by at most 10% (n = 189), while the large uncertainty in estimates from the relatively small American dataset (n = 53) did not support meaningful inference.


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 Vironostika-LS in the repeat donor population.The estimates of the mean recency duration, ω, under both the simultaneous estimation of ω and α, and when using an input α, for T = 1 year, are provided. For the latter estimation, the estimated ω is plotted as a function of the assumed α. The 95% confidence regions (CRs) for ω and α (simultaneous estimation) and confidence intervals (CIs) for ω (assuming α, and not accounting for uncertainty in α) are displayed. Part A shows the results for the South African repeat donor sample, while Part B shows the results for the USA repeat donor sample.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0020027-g001: Estimated RITA characteristics for the Vironostika-LS in the repeat donor population.The estimates of the mean recency duration, ω, under both the simultaneous estimation of ω and α, and when using an input α, for T = 1 year, are provided. For the latter estimation, the estimated ω is plotted as a function of the assumed α. The 95% confidence regions (CRs) for ω and α (simultaneous estimation) and confidence intervals (CIs) for ω (assuming α, and not accounting for uncertainty in α) are displayed. Part A shows the results for the South African repeat donor sample, while Part B shows the results for the USA repeat donor sample.
Mentions: The estimated RITA characteristics (using a threshold of 1) are shown (Fig. 1), for both estimation assuming a known α, and simultaneous estimation of ω and α. Observations with Δi>T = 1 year were used (the maximum duration in the state of recency has been estimated to be 200 days [26] and 1 year [17]), resulting in sample sizes of n = 282 and n = 106 for the South African and American datasets respectively. A comparison of the observed percentages of seroconverters who were recently infected to the expected percentages (by substituting the estimated RITA characteristics into (8)), as functions of ID interval, suggests good agreement under simultaneous estimation of the RITA characteristics (SDC S1, Section C). When exploring the sensitivity of results to T, when T was increased to 2.5 years, estimates from the South African dataset varied by at most 10% (n = 189), while the large uncertainty in estimates from the relatively small American dataset (n = 53) did not support meaningful inference.

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