Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Effects of accounting for interval-censored antibody titer decay on seroincidence in a longitudinal cohort study of leptospirosis
AU - Bonner, K.A.O.
AU - Cruz, J.S.
AU - Sacramento, G.A.
AU - De Oliveira, D.
AU - Nery, N.
AU - Carvalho, M.
AU - Costa, F.
AU - Childs, J.E.
AU - Ko, A.I.
AU - Diggle, P.J.
PY - 2021/5/31
Y1 - 2021/5/31
N2 - Accurate measurements of seroincidence are critical for infections undercounted by reported cases, such as inf luenza, arboviral diseases, and leptospirosis. However, conventional methods of interpreting paired serological samples do not account for antibody titer decay, resulting in underestimated seroincidence rates. To improve interpretation of paired sera, we modeled exponential decay of interval-censored microscopic agglutination test titers using a historical data set of leptospirosis cases traced to a point source exposure in Italy in 1984.We then applied that decay rate to a longitudinal cohort study conducted in a high-transmission setting in Salvador, Brazil (2013-2015). We estimated a decay constant of 0.926 (95% confidence interval: 0.918, 0.934) titer dilutions per month. Accounting for decay in the cohort increased the mean infection rate to 1.21 times the conventionally defined rate over 6-month intervals (range, 1.10-1.36) and 1.82 times that rate over 12-month intervals (range, 1.65-2.07). Improved estimates of infection in longitudinal data have broad epidemiologic implications, including comparing studies with different sampling intervals, improving sample size estimation, and determining risk factors for infection and the role of acquired immunity. Our method of estimating and accounting for titer decay is generalizable to other infections defined using interval-censored serological assays.
AB - Accurate measurements of seroincidence are critical for infections undercounted by reported cases, such as inf luenza, arboviral diseases, and leptospirosis. However, conventional methods of interpreting paired serological samples do not account for antibody titer decay, resulting in underestimated seroincidence rates. To improve interpretation of paired sera, we modeled exponential decay of interval-censored microscopic agglutination test titers using a historical data set of leptospirosis cases traced to a point source exposure in Italy in 1984.We then applied that decay rate to a longitudinal cohort study conducted in a high-transmission setting in Salvador, Brazil (2013-2015). We estimated a decay constant of 0.926 (95% confidence interval: 0.918, 0.934) titer dilutions per month. Accounting for decay in the cohort increased the mean infection rate to 1.21 times the conventionally defined rate over 6-month intervals (range, 1.10-1.36) and 1.82 times that rate over 12-month intervals (range, 1.65-2.07). Improved estimates of infection in longitudinal data have broad epidemiologic implications, including comparing studies with different sampling intervals, improving sample size estimation, and determining risk factors for infection and the role of acquired immunity. Our method of estimating and accounting for titer decay is generalizable to other infections defined using interval-censored serological assays.
KW - 4-fold rise
KW - Antibody
KW - Interval-censored assay
KW - Leptospirosis
KW - Paired serology
KW - Seroconversion
KW - Serological assay
KW - Titer decay
U2 - 10.1093/aje/kwaa253
DO - 10.1093/aje/kwaa253
M3 - Journal article
VL - 190
SP - 893
EP - 899
JO - American Journal of Epidemiology
JF - American Journal of Epidemiology
SN - 0002-9262
IS - 5
ER -