Absence of evidence of transfusion transmission risk of Creutzfeldt-Jakob disease in the United States: Results froma 28-year lookback study.

BACKGROUND: For many years, there has been concern about the risk of transmission of classic forms of Creutzfeldt-Jakob disease (CJD) by blood transfusion, particularly after the recognition of such transmission of variant CJD (vCJD). We report on a 28-year lookback study of recipients of blood from donors who subsequently developed CJD. METHODS: Patients with diagnosed CJD and a history of blood donation were identified. Blood centers were asked to provide information about the distribution of the donations and consignees were requested to provide information about the recipients of the donations. Vital status of each available recipient was determined and, if deceased, the reported cause(s) of death were obtained primarily from the National Death Index. All recipients included in the study database contributed person-time up to the last recorded review of vital status. RESULTS: There were 84 eligible donors who gave 3284 transfusable components, and it was possible to evaluate 1245 recipients, totaling 6495 person-years of observation. The mean observation period per recipient was 5.5 years with a maximum of 51 years. No case of CJD or prion disease was reported among the recipient population. DISCUSSION: The study suggests that CJD may not be transfusion-transmissible, a position in agreement with similar findings from two similar European reports amounting to an overall observation period of 15,500 person-years. These studies have supported the conclusion that the risk, if any, of transmission of CJD by blood products is extremely small and remains theoretical.

HIV risk behavior profiles among men who have sex with men interested in donating blood: Findings from the Assessing Donor Variability and New Concepts in Eligibility study.

BACKGROUND: Individual risk assessment allows donors to be evaluated based on their own behaviors. Study objectives were to assess human immunodeficiency virus (HIV) risk behaviors in men who have sex with men (MSM) and estimate the proportion of the study population who would not be deferred for higher risk HIV sexual behaviors. STUDY DESIGN AND METHODS: Cross-sectional survey and biomarker assessment were conducted in eight U.S. cities. Participants were sexually active MSM interested in blood donation aged 18-39 years, assigned male sex at birth. Participants completed surveys during two study visits to define eligibility, and self-reported sexual and HIV prevention behaviors. Blood was drawn at study visit 1 and tested for HIV and the presence of tenofovir, one of the drugs in oral HIV pre-exposure prophylaxis (PrEP). Associations were assessed between HIV infection status or HIV PrEP use and behaviors, including sex partners, new partners, and anal sex. RESULTS: A total of 1566 MSM completed the visit 1 questionnaire and blood draw and 1197 completed the visit 2 questionnaire. Among 1562 persons without HIV, 789 (50.4%) were not taking PrEP. Of those not taking PrEP, 66.2% reported one sexual partner or no anal sex and 69% reported no new sexual partners or no anal sex with a new partner in the past 3 months. CONCLUSION: The study found that questions were able to identify sexually active, HIV-negative MSM who report lower risk sexual behaviors. About a quarter of enrolled study participants would be potentially eligible blood donors using individual risk assessment questions.

Trajectory and Demographic Correlates of Antibodies to SARS-CoV-2 Nucleocapsid in Recently Infected Blood Donors, United States.

We evaluated antibodies to the nucleocapsid protein of SARS-CoV-2 in a large cohort of blood donors in the United States who were recently infected with the virus. Antibodies to the nucleocapsid protein of SARS-CoV-2 indicate previous infection but are subject to waning, potentially affecting epidemiologic studies. We longitudinally evaluated a cohort of 19,323 blood donors who had evidence of recent infection by using a widely available serologic test to determine the dynamics of such waning. We analyzed overall signal-to-cutoff values for 48,330 donations (average 2.5 donations/person) that had an average observation period of 102 days. The observed peak signal-to-cutoff value varied widely, but the waning rate was consistent across the range, with a half-life of 122 days. Within the cohort, only 0.75% of persons became seronegative. Factors predictive of higher peak values and longer time to seroreversion included increasing age, male sex, higher body mass index, and non-Caucasian race.

COVID-19 convalescent plasma donors: Unique motivations in unique times?

BACKGROUND: Early in the SARS-CoV-2 pandemic, many blood collection organizations (BCOs) were asked to collect and distribute COVID-19 convalescent plasma (CCP) as a potential treatment for this new virus and resulting disease. However, recruiting CCP donors presented unique challenges for BCOs, as there were few recovered patients at this time, and like the general population, most potential CCP donors had no blood donation experience. Thus, many CCP donors were new donors, and their donation motivations were unknown. MATERIALS AND METHODS: Donors who gave CCP at least once between April 27th and September 15th, 2020, were emailed a link to an online survey regarding their experience with COVID-19 and their motivations for donating CCP and blood. RESULTS: Of the 14,225 invitations sent, 3471 donors responded (24.4%). Most donors had never donated blood before (n = 1406), followed by lapsed donors (n = 1050), and recent donors (n = 951). There was a significant relationship between self-reported donation experience and fear of CCP donation (X2  = 119.2, p < .001). Motivations ranked "very important" by responding donors were wanting to help someone in need, a feeling of responsibility, and feeling a duty to donate. Donors with more severe disease were more likely to respond with feelings of a sense of duty to donate CCP (Χ2  = 8.078, p = .044) or altruism (Χ2  = 8.580, p = .035). CONCLUSIONS: Overwhelmingly, altruism and a sense of duty and responsibility were the reasons that CCP donors decided to donate. These insights can be useful for motivating donors for specialized donation programs or if wide scale CCP recruitment is needed in the future.

Low risk of human T-lymphotropic virus infection in U.S. blood donors; Is it time to consider a one-time selective testing approach?

BACKGROUND: U.S. blood donors are tested at each donation for human T-lymphotropic virus (HTLV) antibodies. Depending on donor incidence and other mitigation/removal technologies, a strategy of one-time selective donor testing should be considered. METHODS: Antibody seroprevalence was calculated for HTLV-confirmed-positive American Red Cross allogeneic blood donors from 2008 to 2021. Incidence was estimated for seven 2-year time periods using confirmed-positive repeat donors having seroconverted in 730 days. Leukoreduction failure rates were obtained from internal data from July 1, 2008-June 30, 2021. Residual risks were calculated using a 51-day window period. RESULTS: Between 2008 and 2021, >75 million donations (>18 million donors) yielded 1550 HTLV seropositives. HTLV seroprevalence was 2.05 antibody-positives per 100,000 donations (0.77 HTLV-1, 1.03 HTLV-2, 0.24 HTLV-1/2), and 10.32 per 100,000 among >13.9 million first-time donors. Seroprevalence differed significantly by virus type, sex, age, race/ethnicity, donor status, and U.S. census region. Over 14 years and 24.8 million person-years of observation, 57 incident donors were identified (25 HTLV-1, 23 HTLV-2, and 9 HTLV-1/2). Incidence decreased from 0.30 (13 cases) in 2008-2009 to 0.25 (7 cases) in 2020-2021. Female donors accounted for most incident cases (47 vs. 10 males). In the last 2-year reporting period, the residual risk was 1 per 2.8 million donations and 1 per 3.3 billion donations when coupled with successful leukoreduction (0.085% failure rate). CONCLUSIONS: HTLV donation seroprevalence for the years 2008-2021 varied by virus type and donor characteristics. Low HTLV residual risk and use of leukoreduction processes support the conclusion that a selective one-time donor testing strategy should be considered.

Validity of donor-reported iron supplementation practices obtained at the time of donation.

BACKGROUND: Iron supplementation (IS) improves blood donors' iron stores and allows more frequent blood donation. Understanding the accuracy of self-reported IS is helpful for potential application of IS practices to donor eligibility or donation intervals. METHODS: Successful whole blood and red cell apheresis donors completed a survey at donation on the use of select dietary supplements. Respondents reporting use of either iron pills (IP) or multivitamins (MV) were invited by email to complete a similar follow-up survey 6-8 weeks later and to provide the quantitative iron content of IS by referring the donor to the pill bottle label. Consistency between baseline and follow-up responses was assessed overall and by pill type and demographic variables. RESULTS: Of 2444 donors answering the baseline survey, 40% (978) reported MV or IP at donation, 354 of whom completed the follow-up survey. A majority of survey respondents (56%-61%) reported taking iron across the two surveys, and 21%-24% took MV but were uncertain if their pills contained iron. Of 215 reporting IS at baseline, overall concordance at follow-up was 68% and was higher for donors who were female, ≥50-years old, and taking iron as an iron pill rather than in a multivitamin. CONCLUSION: Consistency of donor responses may be insufficient for use in guiding donor eligibility. Referring donors to their pill bottles was unsuccessful in improving the high frequency of uncertain responses. Incorporating IS into donor eligibility determinations is a complex endeavor that will benefit from careful planning and from post-implementation monitoring.

International survey of strategies to mitigate transfusion-transmitted Trypanosoma cruzi in non-endemic countries, 2016-2018.

BACKGROUND AND OBJECTIVES: Chagas disease, caused by Trypanosoma cruzi, is endemic to Mexico, Central and South America. While initially limited to the Americas, emigration of infected persons triggered geographically broader blood safety challenges. To mitigate transfusion-transmitted Chagas (TTC), transfusion services implemented approaches including risk factor questions and serologic testing. We sought to understand and compare strategies in non-endemic countries. MATERIALS AND METHODS: Transfusion services in International Society of Blood Transfusion (ISBT)-affiliated organizations and members of the ISBT Working Party on Transfusion-Transmitted Infectious Diseases were invited to complete an online survey on T. cruzi mitigation strategies. The survey queried about cases of TTC, risk factors, testing methodology, educational materials, pathogen reduction, donor/product management, donor deferral and perceived public health concerns surrounding TTC. RESULTS: Responses were received from 27 institutions in 22 countries. Most countries (77.3%) reported no historical TTC cases, while 18.2% reported 1-5 cases and 4.5% reported 6-10 cases. Concern about Chagas among the general public and public health authorities was low, but 12 of 25 blood centres reported moderate/high concern. Overall, 17 countries mitigated for TTC: 15 used risk factor questions and 10tested for T. cruzi antibodies. Ten countries used pathogen reduction but not specifically to prevent TTC. CONCLUSION: While Chagas is rarely cited as a public health concern, blood centres in many non-endemic countries, including those outside the Americas, implemented measures to mitigate risk. Mitigation focussed on risk factors associated with Latin American immigrants and serologic testing. Thus, despite the rarity of TTC, many non-endemic countries continue to address it as an ongoing blood safety risk.

COVID-19 convalescent plasma donor characteristics, product disposition, and comparison with standard apheresis donors.

BACKGROUND: With coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) offering an early treatment option for COVID-19, blood collectors needed to quickly overcome obstacles to recruiting and qualifying eligible donors. We provide attributes of CCP donors and products and compare to standard donors and products. STUDY DESIGN AND METHODS: Information on CCP donors was gathered from the American Red Cross qualification website through product collection. Data from 2019 for standard plasma/platelet apheresis (SA) and whole blood (WB) donor demographics and SA donations including product disposition and reactions were used for comparison. RESULTS: Of almost 59 000 donors registering on the website, 75% reported an existing COVID-19 diagnostic polymerase chain reaction or an antibody test. The majority (56.2%) of 10 231 CCP donors were first-time donors in contrast to SA or WB donor populations, which were only 3.0% and 30.6%, respectively, first-time donors. The number of female donors was 12% higher than SA donors. Older (≥ 65 years) and younger (16-19 years) were comparatively underrepresented in CCP donors. Deferral (10.2%) and Quantity Not Sufficient rates (6.4%) for presenting CCP donations were higher than SA (8.2% and 1.1%, respectively). Human leukocyte antigen antibody reactivity was the highest cause of product loss for CCP donations vs SA donations (9.6% vs 1.3%). Acute adverse events also occurred at a higher rate among both first-time and repeat CCP donations compared to SA. CONCLUSIONS: CCP donors were more likely to be first-time and female donors than WB or SA donors. CCP donations had a higher rate of donor adverse reactions, deferrals, and product loss than SA donations.

Effectiveness of the post-donation instruction sheet in conveying information to repeat blood donors.

BACKGROUND AND OBJECTIVES: Written materials are commonly used for blood donor education. While pre-donation materials are largely standardized across US blood collectors, the post-donation instruction sheet (PDIS) is variable and few have been evaluated to assess their effectiveness in conveying information as reflected by donors' attention, understanding and recall. METHODS: An online survey was sent to two independent randomly selected samples of repeat donors, before and after implementation of the enhanced PDIS. RESULTS: A total of 12 935 blood donors responded (33·4% response rate). Most donors did not read the entire PDIS - 34·3% less than half and 18·1% none. Of the 10 593 donors who reported reading any of the PDIS, 97·8% recalled instructions about immediate post-donation care (e.g. extra fluids/no exercise) and 88·0% to call with questions/problems. However, only 50·1% remembered reading about what to do if you felt dizzy/faint and 32·4% about care for bruises. Recall rates in every area were similar before and after revision; except after revision, more donors remembered seeing information about maintaining iron and fewer that you should call the centre back with additional health information (P < 0·0001). DISCUSSION: Blood collectors rely heavily on written materials to convey instructions to donors. Most repeat donors do not read the entire PDIS, and many do not recall important information. More donors recalled seeing how to maintain iron with the enhanced PDIS, but recall deficits remained on how to care for adverse reactions. Written materials alone appear to be insufficient to educate some donors about new or updated topics.

Screening Blood Donors for HIV, HCV, and HBV at the American Red Cross: 10-Year Trends in Prevalence, Incidence, and Residual Risk, 2007 to 2016.

Prevalence, incidence and residual risk of HIV, HCV and HBV are critical indicators of the safety of the blood supply. The American Red Cross routinely monitors these markers. Herein the results of testing over 58 million donations from 2007 to 2016 are reported. The prevalence and incidence of these infections has declined or remained essentially stable over the 7.5 to 10-year period. In 2015 to 2016, the prevalence of HIV, HCV and HBV were respectively: 1.65, 11.47 and 5.85 per hundred thousand (pht) donations with a significant decrease over the 10-year study only for HCV. Weighted incidence rates for all positives were 1.98 pht person years (py) for HIV, 2.20 pht py for HCV and 1.25 pht py for HBV. Estimates of residual risk using these incidence rates were: HIV, 1:2.3 million; HCV, 1:2.6 million; and HBV, 1:1.5 million donations, reflecting very low risk to recipients. There have been increases in the safety of the blood supply compared to prior published estimates. Demographic factors were shown to be associated with variations in infection prevalence and incidence. Continuing changes in the structure of the donor population or changes in policy could impact these measures of safety.

Transfusion-transmitted and community-acquired babesiosis in New York, 2004 to 2015.

BACKGROUND: Babesiosis is a potentially life-threatening zoonotic infection most frequently caused by the intraerythrocytic parasite Babesia microti. The pathogen is usually tickborne, but may also be transfusion or vertically transmitted. Healthy persons, including blood donors, may be asymptomatic and unaware they are infected. Immunocompromised patients are at increased risk for symptomatic disease. STUDY DESIGN AND METHODS: All reported community-acquired babesiosis cases in New York from 2004 to 2015 were evaluated, enumerated, and characterized. All potential transfusion-transmitted babesiosis (TTB) cases reported through one or more of three public health surveillance systems were investigated to determine the likelihood of transfusion transmission. In addition, host-seeking ticks were actively collected in public parks and other likely sites of human exposure to B. microti. RESULTS: From 2004 to 2015, a total of 3799 cases of babesiosis were found; 55 (1.4%) of these were linked to transfusion. The incidence of both community-acquired babesiosis and TTB increased significantly during the 12-year study period. The geographic range of both ticks and tickborne infections also expanded. Among TTB cases, 95% of recipients had at least one risk factor for symptomatic disease. Implicated donors resided in five states, including in 10 New York counties. More than half of implicated donors resided in counties known to be B. microti endemic. CONCLUSION: The increasing incidence of TTB correlated with increases in community-acquired babesiosis and infection of ticks with B. microti. Surveillance of ticks and community-acquired cases may aid identification of emerging areas at risk for Babesia transfusion transmission.

Creutzfeldt-Jakob disease lookback study: 21 years of surveillance for transfusion transmission risk.

BACKGROUND: Transfusion transmission of human prion diseases has been observed for variant Creutzfeldt-Jakob disease (vCJD), but not for the classic forms of prion disease (CJD: sporadic, genetic, and iatrogenic). Although the presence of prions or misfolded prion proteins in blood has been documented in some patients with the most common form of CJD, sporadic CJD, no transfusion-transmitted cases of CJD have been recognized. Since 1995, the American Red Cross has conducted a lookback study of the recipients of blood products from donors who develop CJD to assess the risk of blood-borne CJD transmission in the United States. STUDY DESIGN AND METHODS: Blood donors subsequently diagnosed with confirmed or probable CJD were enrolled and the consignees were asked to identify the recipients of their blood products. These donors' transfusion recipients are traced annually with the National Death Index to see if they subsequently die of CJD. RESULTS: To date, 65 CJD donors have been enrolled along with 826 of their blood recipients. These recipients have contributed 3934 person-years of follow-up and no transfusion-transmitted cases of CJD have been recognized. CONCLUSION: From this study, as well as other epidemiologic studies, there is no evidence of CJD transfusion transmission; this risk remains theoretical.

Standardized Symptom Measurement of Individuals with Early Lyme Disease Over Time.

OBJECTIVE: Understanding the Lyme disease (LD) literature is challenging given the lack of consistent methodology and standardized measurement of symptoms and the impact on functioning. This prospective study incorporates well-validated measures to capture the symptom picture of individuals with early LD from time of diagnosis through 6-months post-treatment. METHOD: One hundred seven patients with confirmed early LD and 26 healthy controls were evaluated using standardized instruments for pain, fatigue, depressive symptoms, functional impact, and cognitive functioning. RESULTS: Prior to antibiotic treatment, patients experience notable symptoms of fatigue and pain statistically higher than controls. After treatment, there are no group differences, suggesting that symptoms resolve and that there are no residual cognitive impairments at the level of group analysis. However, using subgroup analyses, some individuals experience persistent symptoms that lead to functional decline and these individuals can be identified immediately post-completion of standard antibiotic treatment using well-validated symptom measures. CONCLUSIONS: Overall, the findings suggest that ideally-treated early LD patients recover well and experience symptom resolution over time, though a small subgroup continue to suffer with symptoms that lead to functional decline. The authors discuss use of standardized instruments for identification of individuals who warrant further clinical follow-up.

Prevalence, incidence, and risk factors of human immunodeficiency virus infection in blood donors in the Southeastern United States.

BACKGROUND: Human immunodeficiency virus (HIV)-positive blood donors pose a risk to blood safety. The Southeastern United States has the highest reported HIV infection rates. Here we calculate HIV prevalence, incidence, and residual risk in Southeastern US blood donors and report risk factors disclosed by incident donors in counseling sessions. STUDY DESIGN AND METHODS: American Red Cross donation and testing data from 2009 to 2014 for three Southeastern collection regions were used to calculate HIV prevalence, incidence, and residual risk. Incident donors had a previous HIV-negative donation within 730 days of their positive donation. Residual risk was defined as the window period multiplied by incidence. RESULTS: From 2009 to 2014, a total of 236 HIV-positive donors occurred in these regions for an overall prevalence of 8.3 per 100,000 donations. There were 56 incident donors over the 6-year period with incidence decreasing from 7.1 per 100,000 person-years (PYs) in the first two years (2009-2010) to 3.5 in the last two years (2013-2014). Residual risk decreased from 1 in 562,000 to 1 in 1,100,000. The most commonly reported risk factor behavior in male incident donors was men who have sex with men; females expressed no predominant risk factor. CONCLUSION: HIV prevalence and incidence among blood donors in the southeast are higher than other US regions, consistent with general public health surveillance. However, the overall residual risk estimates are low at less than 1 per million. Ongoing monitoring of the blood supply along with educational efforts to provide infected individuals with alternatives to donation remain important initiatives.

CCL19 as a Chemokine Risk Factor for Posttreatment Lyme Disease Syndrome: a Prospective Clinical Cohort Study.

Approximately 10% to 20% of patients optimally treated for early Lyme disease develop persistent symptoms of unknown pathophysiology termed posttreatment Lyme disease syndrome (PTLDS). The objective of this study was to investigate associations between PTLDS and immune mediator levels during acute illness and at several time points following treatment. Seventy-six participants with physician-documented erythema migrans and 26 healthy controls with no history of Lyme disease were enrolled. Sixty-four cytokines, chemokines, and inflammatory markers were measured at each visit for a total of 6 visits over 1 year. An operationalized definition of PTLDS incorporating symptoms and functional impact was applied at 6 months and 1 year following treatment completion, and clinical outcome groups were defined as the return-to-health, symptoms-only, and PTLDS groups. Significance analysis of microarrays identified 7 of the 64 immune mediators to be differentially regulated by group. Generalized logit regressions controlling for potential confounders identified posttreatment levels of the T-cell chemokine CCL19 to be independently associated with clinical outcome group. Receiver operating characteristic analysis identified a CCL19 cutoff of >111.67 pg/ml at 1 month following treatment completion to be 82% sensitive and 83% specific for later PTLDS. We speculate that persistently elevated CCL19 levels among participants with PTLDS may reflect ongoing, immune-driven reactions at sites distal to secondary lymphoid tissue. Our findings suggest the relevance of CCL19 both during acute infection and as an immunologic risk factor for PTLDS during the posttreatment phase. Identification of a potential biomarker predictor for PTLDS provides the opportunity to better understand its pathophysiology and to develop early interventions in the context of appropriate and specific clinical information.

Characteristics of seroconversion and implications for diagnosis of post-treatment Lyme disease syndrome: acute and convalescent serology among a prospective cohort of early Lyme disease patients.

Two-tier serology is often used to confirm a diagnosis of Lyme disease. One hundred and four patients with physician diagnosed erythema migrans rashes had blood samples taken before and after 3 weeks of doxycycline treatment for early Lyme disease. Acute and convalescent serologies for Borrelia burgdorferi were interpreted according to the 2-tier antibody testing criteria proposed by the Centers for Disease Control and Prevention. Serostatus was compared across several clinical and demographic variables both pre- and post-treatment. Forty-one patients (39.4%) were seronegative both before and after treatment. The majority of seropositive individuals on both acute and convalescent serology had a positive IgM western blot and a negative IgG western blot. IgG seroconversion on western blot was infrequent. Among the baseline variables included in the analysis, disseminated lesions (p < 0.0001), a longer duration of illness (p < 0.0001), and a higher number of reported symptoms (p = 0.004) were highly significantly associated with positive final serostatus, while male sex (p = 0.05) was borderline significant. This variability, and the lack of seroconversion in a subset of patients, highlights the limitations of using serology alone in identifying early Lyme disease. Furthermore, these findings underline the difficulty for rheumatologists in identifying a prior exposure to Lyme disease in caring for patients with medically unexplained symptoms or fibromyalgia-like syndromes.

Serum inflammatory mediators as markers of human Lyme disease activity.

Chemokines and cytokines are key signaling molecules that orchestrate the trafficking of immune cells, direct them to sites of tissue injury and inflammation and modulate their states of activation and effector cell function. We have measured, using a multiplex-based approach, the levels of 58 immune mediators and 7 acute phase markers in sera derived from of a cohort of patients diagnosed with acute Lyme disease and matched controls. This analysis identified a cytokine signature associated with the early stages of infection and allowed us to identify two subsets (mediator-high and mediator-low) of acute Lyme patients with distinct cytokine signatures that also differed significantly (p<0.0005) in symptom presentation. In particular, the T cell chemokines CXCL9 (MIG), CXCL10 (IP-10) and CCL19 (MIP3B) were coordinately increased in the mediator-high group and levels of these chemokines could be associated with seroconversion status and elevated liver function tests (p = 0.027 and p = 0.021 respectively). There was also upregulation of acute phase proteins including CRP and serum amyloid A. Consistent with the role of CXCL9/CXCL10 in attracting immune cells to the site of infection, CXCR3+ CD4 T cells are reduced in the blood of early acute Lyme disease (p = 0.01) and the decrease correlates with chemokine levels (p = 0.0375). The levels of CXCL9/10 did not relate to the size or number of skin lesions but elevated levels of serum CXCL9/CXCL10 were associated with elevated liver enzymes levels. Collectively these results indicate that the levels of serum chemokines and the levels of expression of their respective chemokine receptors on T cell subsets may prove to be informative biomarkers for Lyme disease and related to specific disease manifestations.

Development of a foundation for a case definition of post-treatment Lyme disease syndrome.

OBJECTIVES: The study objective is to demonstrate the clinical and research utility of an operationalized definition of post-treatment Lyme disease syndrome (PTLDS), as proposed by the Infectious Diseases Society of America. METHODS: Seventy-four patients with confirmed erythema migrans and 14 controls were enrolled. Patient-reported symptoms and health function (SF-36) were collected pre-treatment and at follow-up visits over 6 months post-treatment. RESULTS: Eight (11%) patients met our operationalized definition of PTLDS, which included self-reported symptoms of fatigue, widespread musculoskeletal pain or cognitive complaints, and functional impact as measured by a T score of <45 on the composite SF-36. No controls met the functional impact criteria. Forty-three (60% patients returned to their previous health status when measured at 6 months post-treatment. Twenty (28%) patients had either residual symptoms or functional impact, but not both, and did not meet criteria for PTLDS. CONCLUSIONS: This operationalized definition of PTLDS allows for identification of those patients who are treated for early Lyme disease and have significant post-treatment illness, as they have both residual symptoms and impact on daily life functioning. With further refinement and improvement of this operationalized definition, the true incidence of PTLDS can be determined and future studies can be designed to examine its pathophysiology and treatment.

Post-treatment Lyme disease syndrome symptomatology and the impact on life functioning: is there something here?

PURPOSE: A subset of patients treated for Lyme disease report persistent or recurrent symptoms of unknown etiology named post-treatment Lyme disease syndrome (PTLDS). This study aims to describe a cohort of participants with early, untreated Lyme disease, and characterize post-treatment symptomatology and functional impact of PTLDS over time. METHODS: Sixty-three participants with erythema migrans and systemic symptoms were enrolled in a prospective cohort study. Participants underwent physical exams and clinical assessments, and completed the SF-36 (daily life functioning) and the Beck Depression Inventory, Second Edition (BDI-II) (depression), at each of five visits over a period of 6 months. RESULTS: Signs of Lyme disease disappeared post-treatment; however, new-onset patient-reported symptoms increased or plateaued over time. At 6 months, 36% of patients reported new-onset fatigue, 20% widespread pain, and 45% neurocognitive difficulties. However, less than 10% reported greater than "minimal" depression across the entire period. Those with PTLDS (36%) did not differ significantly from those without with respect to demographics, pre-treatment SF-36, and BDI-II scores. Statistically significant differences were found over time on the Role Physical, Vitality, Social Functioning, Role Emotional, and Mental Health subscales (with a trend toward significance for the remaining three subscales of Physical Functioning, Bodily Pain, and General Health) of the SF-36 between those with an eventual PTLDS diagnosis and those without when measured at 6 months. CONCLUSIONS: Unlike clinical signs of Lyme disease, new-onset symptoms are reported by a subset of participants without evidence of depressive symptomatology. Patients who developed PTLDS had significantly lower life functioning compared to those without PTLDS. We propose future avenues for researching infection-triggered symptoms resulting from multiple mechanisms.

Bull's-Eye and Nontarget Skin Lesions of Lyme Disease: An Internet Survey of Identification of Erythema Migrans.

Introduction. Lyme disease is an emerging worldwide infectious disease with major foci of endemicity in North America and regions of temperate Eurasia. The erythema migrans rash associated with early infection is found in approximately 80% of patients and can have a range of appearances including the classic target bull's-eye lesion and nontarget appearing lesions. Methods. A survey was designed to assess the ability of the general public to distinguish various appearances of erythema migrans from non-Lyme rashes. Participants were solicited from individuals who visited an educational website about Lyme disease. Results. Of 3,104 people who accessed a rash identification survey, 72.7% of participants correctly identified the classic target erythema migrans commonly associated with Lyme disease. A mean of 20.5% of participants was able to correctly identify the four nonclassic erythema migrans. 24.2% of participants incorrectly identified a tick bite reaction in the skin as erythema migrans. Conclusions. Participants were most familiar with the classic target erythema migrans of Lyme disease but were unlikely to correctly identify the nonclassic erythema migrans. These results identify an opportunity for educational intervention to improve early recognition of Lyme disease and to increase the patient's appropriate use of medical services for early Lyme disease diagnosis.