Editor: Deborah Sesok-Pizzini, MD, MBA, adjunct professor, Department of Clinical Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Seasonal increase in syphilis screening reactivity rates in whole blood donors
January 2025—The Food and Drug Administration published a letter in December 2021 detailing the risk of false-positive rapid plasma reagin test results when using Bio-Rad Laboratories’ BioPlex 2200 Syphilis Total and RPR kit to test people who had received the COVID-19 vaccine. It did not appear that Treponema pallidum particle agglutination assays were impacted by this issue. Several U.S. and Canadian blood collection organizations noted an unconfirmed increase in syphilis screening test reactivity rates, including unconfirmed repeat reactive rates, during the COVID-19 pandemic. In an investigation of this issue at the authors’ institution, which involved assessing syphilis testing records, the authors saw no change in nontreponemal testing results but did observe an incidental increase in test reactivity with the Beckman Coulter PK TP Microhemagglutination assay for detecting T. pallidum antibodies in 2020 and 2021. The authors conducted a study to explore the false-positive syphilis results using a different institutional assay and calculate the reactivity rate of syphilis screening with negative confirmatory testing from 2011 to 2023. They performed a retrospective study of routine syphilis testing of whole blood collections at an academic hospital-based donor center in the Eastern United States. The authors evaluated all whole blood donations from 2011 to 2023 that showed reactive syphilis screening using the Beckman Coulter PK TP Microhemagglutination test and performed confirmatory tests using the Trinity Biotech Captia Syphilis (T. pallidum)-G enzyme immunoassay. The reactivity rates by year and season of donation were then compared using unpaired t-tests. A total of 109 whole blood donations from 86 unique donors screened reactive for syphilis with negative confirmatory testing from 2011 to 2023. This resulted in an unconfirmed syphilis reactivity rate increase from 2018 to 2023 (mean, 0.360 percent) compared to 2011 to 2017 (mean, 0.71 percent; p < .05). Of interest, an autumnal seasonal peak in unconfirmed syphilis reactive tests was noted in fall 2021. It was the season with the highest number of unconfirmed positive whole blood donations. No changes to the testing assay were made during this time. The authors concluded that the unconfirmed syphilis reactivity rate among whole blood donors at their institution increased significantly since 2017 compared with the seven years prior and doubled from 2020 to 2021. The peak in unconfirmed syphilis-positive results in autumn suggests an environmental trigger, such as viral infection or vaccination. Reporting these types of issues with blood donor screening is important for public health and ensuring the reliability and accuracy of testing.
Miller MJ, Long JO, Conry-Cantilena K, et al. Seasonal increase in syphilis screening reactivity rates in whole blood donors, United States, 2011–2013. Transfusion. 2024;64:1623–1627.
Correspondence: Dr. Maureen J. Miller at maureen.miller@nih.gov
Association of urinary cadmium concentration with cognitive impairment in adults
The causative nature of long-term neurodegenerative disease remains elusive, and dementia is a large economic burden on families and society as a whole. Because effective treatments for dementia are lacking, research efforts are shifting to identifying modifiable risk factors to prevent early cognitive decline as a primary prevention for dementia. Cadmium, a highly toxic heavy metal that can be harmful even at low doses, is linked to cognitive impairment and dementia. It is widely discharged into the environment by industrial and agricultural activities and can be found in the air, food, water, and soil. Cadmium can enter the body via multiple routes, including diet, inhalation of polluted air, and cigarette smoke and can be accumulated over a lifetime because of slow excretion. It has toxic effects on the central nervous system by penetrating the blood-brain barrier, accumulating in the brain, and activating signaling pathways related to oxidative stress, inflammation, and neuronal apoptosis. Studies of long-term longitudinal cohorts that involve cadmium exposure and cognitive performance over time are limited. However, some studies have reported that racial and ethnic differences significantly impact the association of cadmium exposure with various health conditions, including low bone mineral density and prostate cancer. The authors conducted a study to prospectively examine the association between baseline cadmium exposure measured in urine and the incidence of cognitive impairment in a cohort of Black and white American adults, with an average follow-up of 10 years. They used a random subcohort of participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, an ongoing population-based prospective cohort study that enrolled Black and white U.S. adults aged 45 years or older at baseline. The participants, who were free of cognitive impairment or stroke at baseline, had certain trace element concentrations, including urinary creatinine-corrected cadmium, measured using biospecimens collected at baseline and stored. During an average of 10 years of follow-up, global cognitive impairment was assessed annually, and domain-based cognitive impairment, including verbal learning, memory, and executive function, was evaluated every other year using the enhanced cognitive battery. The association between urinary cadmium concentration and the odds of global or domain-based cognitive impairment was examined using multivariable-adjusted logistic regression models. The results showed that out of 2,172 participants (mean age, 64.1 ± 9.0 years; female, 54.8 percent; Black, 38.7 percent) with available data on urinary cadmium concentrations, there were 195 cases of global cognitive impairment and 53 cases of domain-based cognitive impairment. No association between cadmium and cognitive impairment was found in the full sample. However, a significant positive association between urinary cadmium concentration and global cognitive impairment was noted among white study participants. Of interest, the odds of cognitive impairment for white participants in the high urinary cadmium concentration group (median or higher) were approximately double those in the low urinary cadmium group (odds ratio, 2.07; 95 percent confidence interval, 1.18–3.64). Factors such as sex, age, region, smoking pack-years, alcohol consumption, and levels of other related metals did not have a significant impact on the analysis. The authors determined that a synergistic effect between cadmium and smoking cannot be ruled out and that the statistical power of the study when analyzing the data from never smokers by race was insufficient. Furthermore, because the study evaluated urinary cadmium, it may not fully reflect the cadmium burden in tissue, including the lungs. The authors concluded that the findings from this prospective cohort suggest that urinary cadmium concentrations are associated with global cognitive impairment among white but not Black people. The authors noted that additional studies with repeatedly measured cadmium exposure, larger samples sizes, and longer duration will help inform further research and the racial discrepancy observed in this study.
Lu L, Zhang Y, Angley M, et al. Association of urinary cadmium concentration with cognitive impairment in US adults. Neurology. 2024;103(7). doi:10.1212/WNL.0000000000209808
Correspondence: Dr. Ka Kahe at kk3399@columbia.edu