Detection of unreported usage of the antiretroviral drug lamivudine in two blood donors.

BACKGROUND: Unreported HIV antiretroviral (ARV) drug usage by blood donors compromises the ability to detect evidence of HIV infection in blood screening tests and represents a risk for blood transfusion safety. Our objective was to determine the frequency of undeclared ARV drug use by blood donors with altered HIV markers. STUDY DESIGN AND METHODS: This was a retrospective cross-sectional analysis of donations that were tested for HIV antibody (ab), antigen (ag), and RNA by chemiluminescent immunoassay and nucleic acid screening tests. Positive samples were retested and were subjected to ARV drug testing by high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Of 345,252 blood donations, 361 (0.1%) were positive on initial testing. Samples from 296 (81.9%) of these donations were available for further analysis. The presence of HIV ab/ag and/or RNA was confirmed in 83 (28.0%) of these samples. All 296 bloods were subjected to ARV testing. The ARV drug lamivudine, at 11.3 and 6.7 ng/mL, was detected in 2 of 83 (2.4%) donations that were HIV positive. Other drugs were not detected. CONCLUSION: Unreported ARV usage was identified in two candidates for blood donation. More intensive efforts to educate donors about disclosure and to investigate the extent of this phenomenon in Brazil are needed.

Improved detection of hepatitis C virus-positive blood donors and determination of infection status.

BACKGROUND: In low-risk populations, variability in the sensitivity of current serological tests for Hepatitis C virus (HCV) blood donor screening may lead to the presence of false-positive results. This contributes to the unnecessary loss of blood donor samples as well as to difficulty in accurate donor counselling. The present study determined the optimal cut-off value of a chemiluminescent immunoassay for identification of HCV-reactive blood donors. STUDY DESIGN AND METHODS: In a retrospective cross-sectional analysis of 193 973 blood donations, 578 samples that were positive for HCV antibody in a chemiluminescent immunoassay and/or RNA screening tests were identified. Blood from 379 of these positive samples was available for retesting by a second confirmatory HCV immunoassay followed by a receiver operating characteristic (ROC) curve analysis. Donors were also recalled for a new analysis. RESULTS: Only 71 (18.7%) blood samples remained HCV-positive upon retesting, while 233 (61.5%) now tested negative and 75 (19.8%) yielding indeterminate results. A signal to cutoff ratio ≥4.32 was determined as the best differential threshold between a positive and negative result, increasing the positive predictive value from 27.3% to 66.7%. CONCLUSION: Using a higher threshold for an HCV-positive blood sample enhances the chemiluminescent immunoassay screening test´s accuracy and helps to improve donor counselling and notification processes.

External quality control program in infectious diseases screening at laboratories and blood banks in Latin America: an analysis of the past 5 years.

Objective: To evaluate the screening of blood samples for infectious disease markers at laboratories and blood banks in Latin America per the findings of an External Quality Assessment Program (EQAP). Methods: This qualitative analysis used data from the EQAP coordinated by the Fundação Pro Sangue Hemocentro de São Paulo with the support of the Pan American Health Organization to assess the performance of blood screening for infectious diseases from 2014 to 2018 in Latin America. Each participating laboratory or blood bank received an identical blind panel with 24 blood samples with variable reactivity for all the screening parameters. Panels were processed at each participating facility and results were returned to the Fundação Pro Sangue Hemocentro de São Paulo for individual and joint analyses. Two types of discrepant results were potential failures: false positive results (FPRs) and false nonreactive results (FNRRs). Results: A total of 23 136 samples were evaluated. Global rates of FPR, FNRR, and concordant results were 0.3%, 1.0% and 98.7%, respectively. Seven FNRRs were found for HBsAg (1.0%), 12 for syphilis (2.6%), and 21 for Chagas disease (2.9%). No FNRRs were found for the HIV, HCV, and HTLV viruses. The average accuracy of all the laboratories and blood banks participating in the EQAP during the study period was 99.5% (standard deviation, 0.5%). Conclusion: The findings of this qualitative analysis are positive for blood safety in Latin America, with an average accuracy of 99.5% among the participating laboratories and blood banks. This report reflects an important improvement in blood bank serological screening EQAP-PAHO report since the 2003.

Influence of unreported HIV prophylaxis on the kinetics of post-blood donation HIV seroconversion.

BACKGROUND: In 2020, of 110,000 blood donors screened for HIV exposure two individuals were identified who were viral RNA-positive but seronegative. One of the donors, borderline negative in a pooled screening test for HIV RNA, utilized antiretroviral drugs as post-exposure, pre-donation prophylaxis. The kinetics of subsequent HIV seropositivity in both donors are described. STUDY DESIGN AND METHODS: Both donors were recalled and interviewed, and blood was obtained at intervals for HIV antibodies and RNA testing. RESULTS: One donor used antiretroviral prophylaxis for 30 days due to a relationship with an HIV-positive partner. In follow-up samples, seroconversion was noted at 70 days, and viral RNA was detected at 105 days, after blood donation. In contrast, the other donor seroconverted in <25 days and the appearance and titer of HIV RNA was in accordance with the typical pre-seroconversion window. CONCLUSION: The use of anti-viral prophylaxis by blood donors in the acute phase of HIV infection delays seroconversion. A 6-month deferral in blood donation after HIV prophylaxis, as currently recommended in Brazil, would have been sufficient in this case to mitigate the risk of transfusion-transmitted HIV. Ultimately, improvement in donor compliance with selection procedures for blood donation is needed to optimize blood safety.

Occult and active hepatitis B virus detection in donated blood in São Paulo, Brazil.

BACKGROUND: The present study determined the HBV antigen, antibody, and DNA status in blood donations deemed to be HBV positive. Individuals with an occult HBV infection (OBI), defined as being positive for HBV DNA but negative for HBV surface antigen (HBsAg), as well as those with active infection (HBsAg-positive), were identified and characterized. STUDY DESIGN AND METHODS: From a total pool if 198,363 blood donations, we evaluated in a cross-sectional study, 1106 samples that were positive in screening tests for antibody to HBV core antigen (HBcAb), HBsAg, and/or HBV DNA by nucleic acid testing (NAT-HBV). The presence of genetic variants in the HBV pol/S gene in individuals with an active HBV infection was also determined. RESULTS: OBIs were detected in six of 976 samples (0.6%) that were positive only for HBcAb. The rate of HBV active infection was 0.024% (48/198,363) and there was a predominance of HBV sub-genotype A1 (62.2%, 28/45), followed by D3 (17.8%, 8/45). Mutations in the S gene were found in 57.8% (26/45) and immune escape mutations in 37.8% (17/45) of active HBV-infected donors. Among them, T123N, G145A, and D144G high-impact immune escape mutations were identified. CONCLUSION: Highly sensitive molecular tests improve the capacity to detect OBIs. When NAT is performed in pooled samples, HBcAb test has value in the detection of donors with OBI and improves transfusion safety. Mutations in the S gene are frequent in HBsAg-positive blood, including those associated with diagnostic failure and vaccine escape mutations.

Correlation between SARS-COV-2 antibody screening by immunoassay and neutralizing antibody testing.

BACKGROUND: The efficacy of convalescent plasma (CP), an alternative for the treatment of COVID-19, depends on high titers of neutralizing antibodies (nAbs), but assays for quantifying nAbs are not widely available. Our goal was to develop a strategy to predict high titers of nAbs based on the results of anti-SARS-CoV-2 immunoassays and the clinical characteristics of CP donors. STUDY DESIGN AND METHODS: A total of 214 CP donors were enrolled and tested for the presence of anti-SARS-CoV-2 antibodies (IgG) using two commercial immunoassays: EUROIMMUN (ELISA) and Abbott (Chemiluminescence). Quantification of nAbs was performed using the Cytopathic Effect-based Virus Neutralization test. Three criteria for identifying donors with nAbs ≥ 1:160 were tested: - C1: Curve ROC; - C2: Conditional decision tree considering only the IA results and - C3: Conditional decision tree including both the IA results and the clinical variables. RESULTS: The performance of the immunoassays was similar referring to both S/CO and predictive value for identifying nAbs titers ≥1:160. Regarding the studied criteria for identifying CP donors with high nAbs titers: (a) C1 showed 76.1% accuracy if S/CO = 4.65, (b) C2 presented 76.1% accuracy if S/CO ≥4.57 and (c) C3 had 71.6% accuracy if S/CO was ≥4.57 or if S/CO was between 2.68-4.57 and the last COVID-19-related symptoms were recent (within 19 days). CONCLUSION: SARS-CoV-2 IgG immunoassays (S/CO) can be used to predict high anti-SARS-CoV-2 nAbs titers. This study has proposed different criteria for identifying donors with ≥1:160 nAbs titers, all with high efficacy.

Detection and analysis of blood donors seropositive for syphilis.

BACKGROUND: The increasing incidence of syphilis worldwide has called attention to the risk of transmission by transfusion. AIMS: To determine the prevalence of active syphilis in blood donors and characterise the serological profile of syphilis-positive donors. METHODS: Samples positive for Treponema pallidum using the chemiluminescent microparticle immunoassay (CMIA) during blood donor screening from 2017 to 2018 were tested by the Venereal Disease Research Laboratory (VDRL) non-treponemal test and for anti-T. pallidum IgM by ELISA (Immunoassay Enzyme test for detection of IgM antibodies). The INNO-LIA Syphilis test (Line Immuno Assay solid test for confirmation antibodies to Treponema pallidum) was performed as a confirmatory test on samples that were positive on ELISA-IgM but negative on VDRL. ELISA-IgM (+) samples were also tested for T. pallidum DNA in sera by real-time polymerase chain reaction (PCR). RESULTS: Of 248 542 samples screened, 1679 (0.67%) were positive for syphilis by CMIA. Further analysis was performed on 1144 (68.1%) of these samples. Of those tested, 16% were ELISA IgM(+)/VDRL(+), 16.5% were ELISA IgM(-)/VDRL(+), 4.1% were ELISA IgM(+)/VDRL(-), and 63.4% were ELISA IgM (-)/VDRL(-). The INNO-LIA Syphilis test results were 33 (3%) positive, 2 (0.2%) undetermined and 12 (1%) negative. Of the 230 EIA-IgM(+) samples (20.1%), 5 (2.2%) were PCR positive. The prevalence of active syphilis in 2017 and 2018 was 0.1% and 0.07%, respectively, and overall prevalence of serologic markers for syphilis was highest among male, unmarried, 25-34-year-olds with a high school education and who were first-time donors. CONCLUSION: There is a risk of transfusion-transmitted syphilis in blood banks that exclusively use the VDRL test for donor screening, as is currently the situation in some Brazilian blood centres, as well as in other blood centres around the world.

Hepatitis B virus among hematopoietic stem cell transplant recipients: Antiviral impact in seroconversion, engraftment, and mortality in a Latin American center.

BACKGROUND: Hepatitis B virus (HBV) infection is a worldwide concern with a broad distribution. In immunosuppressed populations, such as solid organ and hematopoietic stem cell transplant (HSCT) recipients, it can reactivate leading to acute hepatic failure. Different risk factors are known for higher rates of reactivation, and entecavir, tenofovir, and lamivudine are often used for prophylaxis and treatment. However, data regarding the impact of antiviral drugs in neutrophil and platelet engraftment are still unknown and concern the management of viral hepatitis post-HSCT. METHODS: We performed a single-center, retrospective, observational study reviewing medical records of patients referred for hematopoietic stem cell transplant from 2010 to 2017, which were also HBV infected, aiming to describe outcomes related to antiviral treatment and also the impact on platelet and neutrophil recovery after transplant. A secondary goal consisted of analyzing the impact of HBV infection in early and late mortality post-HSCT. The study included patients with positive blood bank screening for hepatitis B infection (HBsAg, Anti-HBc or HBV-NAT), confirmed later on by a laboratory routine serology. RESULTS: A total of 1132 hematopoietic stem cell recipients were assessed between 2010 and 2017. Eighty-six patients were confirmed to have HBV infection, of which six were HBsAg-positive, 20 were isolated anti-HBc-positive, and 60 had resolved infection (anti-HBc-positive and anti-HBs-positive). With regard to prophylaxis, 19 patients underwent HSCT on HBV antiviral therapy or prophylaxis: two were HBeAg-positive, three were HBeAg-negative and HBV-DNA was only detectable in three of them. Moreover, one patient had an occult HBV infection. Regarding therapy, 9 patients were on entecavir, 6 patients on lamivudine, two on tenofovir, and two of them on a combination of tenofovir + lamivudine due to HIV co-infection. Reverse seroconversion was not identified in any patients receiving antiviral therapy or prophylaxis, but it was detected in one patient with occult hepatitis B and another with resolved infection. No severe side effects led to therapy discontinuation in the treated group, which also did not have any significant delay in neutrophil or platelet engraftment when compared to patients without antiviral therapy. In addition, the only factors associated with increased mortality were transplant onset after 50 years, allogeneic transplant and myeloablative conditioning regimens. Interestingly, the presence of HBsAg or detectable HBV-DNA was not related to worse outcomes, neither the use of rituximab. In multivariate analysis, the use of antiviral therapy, the occurrence of graft-versus-host disease or CMV reactivation also was not linked to increased mortality. CONCLUSIONS: To sum up, HBV serology, ALT, and HBV-DNA monitoring are essential to detect hepatic flares earlier, even in populations with chronic inactive hepatitis, due to the possibility of later seroconversion. HBV infection was not related to increased 2-year mortality post-transplant. Antiviral prophylaxis did not cause any important clinical or laboratory side effects that could demand discontinuation, and its use was not associated with later neutrophil and platelet engraftments.

Using droplet digital PCR to screen for rare blood donors: Proof of principle.

BACKGROUND: Digital droplet PCR (ddPCR) is a very sensitive high throughput genotyping methodology. To date, the use of ddPCR in immunohematology is restricted to fetal genotyping of red blood cell antigens. Our hypothesis is that this technology could be applied to screen for rare red blood cell genotypes, such as Di(b-). METHODS: Nucleic acid of 3168 donors was extracted for viral screening routine in pools of 6, which were converted into three types of 48-donor pools: control pools (only DI*B/*B samples), pools with varying amount of DI*A/*B samples (n = 1-5) and a pool with one rare DI*A/*A sample. Pools were genotyped using ddPCR to detect and quantify DI*A and DI*B alleles. RESULTS: DI*A allele was accurately detected in all pools containing Di(a + b+) samples and in the pool containing one Di(a + b-) sample. No copies were detected in the control pools (n = 60). The ratio between the number of DI*A and DI*B copies varied significantly between the pools and the triplicates. CONCLUSION: The proposed ddPCR assay was accurate in identifying the rare DI*A allele in large pools of donors and can be applied to screen for Di(b-) phenotype. The strategy can potentially be extended to search for other rare RBC phenotypes.

SMIM1 intron 2 gene variations leading to variability in Vel antigen expression among Brazilian blood donors.

BACKGROUND: There is a significant inter-individual heterogeneity of Vel antigen expression which can lead to inaccuracies on Vel phenotyping of blood donors and, potentially, to hemolytic post-transfusion reactions. Our aim was to evaluate the impact of genetic variants in the SMIM1 intron 2 on the expression of Vel antigen among Brazilian blood donors harboring the c.64_80del17 deletion in heterozygosity. METHODS: Donors presenting the SMIM1 c.64_80del17 in heterozygosity were included in the study and subjected to SMIM1 intron 2 direct sequencing aiming to genotype the following polymorphisms: rs143702418, rs1181893, rs191041962, rs6673829, rs1175550 and rs9424296. RESULTS: SMIM1 intron 2 sequencing was performed on two hundred donors presenting one c.64_80del17 allele. The rs1175550 polymorphism significantly impacted on Vel antigen expression. Variations in the strength of agglutination on Vel phenotyping were also observed according to the rs6673829 genotype, but this difference did not persist with statistical relevance after multivariate analysis. CONCLUSION: The presence of the rs1175550A allele of SMIM1 is significantly and independently associated with a decrease in Vel antigen expression. Even though the population in Brazil is intensely mixed, the allele frequencies obtained in the current study were very similar to that reported for Europeans.

High-throughput strategy for molecular identification of Vel- blood donors employing nucleic acids extracted from plasma pools used for viral nucleic acid test screening.

BACKGROUND: Serologic methods to determine the Vel- phenotype require the use of rare human antisera and do not allow for many samples to be tested simultaneously, which limits their application as a tool to search for rare donors. This study developed a low-cost molecular screening strategy using real-time polymerase chain reaction (PCR) and DNA, extracted from plasma pools for viral nucleic acid test (NAT) screening, to identify Vel- and Vel+(W) donors. STUDY DESIGN AND METHODS: A total of 4680 blood donors from the Brazilian southeast region were genotyped through real-time PCR targeting the 17-nucleotide (c.64_80del) deletion in the SMIM1 gene, which determines the Vel- phenotype, by using remaining nucleic acid from plasma pools of six donors, routinely discarded after the release of viral NAT results. RESULTS: Twenty pools tested reactive and individual testing of samples from reactive pools identified 19 heterozygous donors with the SMIM1*64_80del deletion (0.40%) and one homozygous donor (0.02%). Fourteen of the 19 donors were confirmed as Vel- or Vel+(W) using anti-Vel human antiserum. CONCLUSION: The DNA pool genotyping strategy using real-time PCR designed to detect the deletion in the SMIM1 gene proved effective and accurate in identifying donors with the Vel- and Vel+(W) phenotypes. The fact that remaining nucleic acid from routine viral NAT screening was used makes this technique economically attractive and definitely superior to the serologic techniques available to search for this rare phenotype.

Real-time symptomatic case of transfusion-transmitted dengue.

BACKGROUND: Dengue virus transmission by blood transfusion is a rarely reported event. CASE REPORT: During a dengue outbreak in São Paulo city, a regular plateletpheresis donor informed the blood bank of being diagnosed a few days after donation. The recipient was hospitalized and displayed symptoms and laboratory evidence of dengue after transfusion. RESULTS: The donor was immunoglobulin (Ig)G, IgM, and polymerase chain reaction nonreactive on the index sample, seroconverting 20 days later. The platelet units were transfused into two patients. One of them developed fever 3 days after transfusion, with high viral load. His pretransfusion sample was negative for IgG, IgM, and dengue RNA, while the second recipient did not show any symptoms nor laboratory evidence of dengue infection. CONCLUSIONS: This case brings additional evidence that dengue is indeed transmissible by blood transfusion and clinical manifestations, although rare, do occur.

Does offering human immunodeficiency virus testing at the time of blood donation reduce transfusion transmission risk and increase disclosure counseling? Results of a randomized controlled trial, São Paulo, Brazil.

BACKGROUND: In a randomized controlled trial (RCT) in a blood bank in São Paulo, we tested the hypotheses that offering client-centered human immunodeficiency virus (HIV) counseling and testing to blood donors would: 1) reduce the risk of HIV contamination in the blood supply by diverting higher-risk, test-seeking donors away from donation and 2) increase return for results and referrals to care. STUDY DESIGN AND METHODS: We randomly selected weeks between August 2012 and May 2013 when donors were offered HIV counseling and testing (n = 6298), leaving usual procedure weeks as control (n = 5569). RESULTS: Few candidate donors chose HIV testing (n = 81, 1.3%). There was no significant difference in herpes simplex virus Type 2 (HSV-2) prevalence (a marker of sexual risk) among donors during intervention weeks compared to control (10.4% vs. 11.1%, p = 0.245). No donor choosing testing was HIV infected, and there was no difference in HSV-2 prevalence between testers and donors (9.9% vs. 10.4%, p = 0.887). Returning for positive results did not differ between testers and donors (three of three vs. 58 of 80, p = 0.386). A higher proportion of donors acknowledged that HIV testing was a strong motivation to donate during intervention weeks compared to control (2.6% vs. 2.0%, p = 0.032). CONCLUSION: The evidence of our RCT is that offering HIV counseling and testing at the time of donation would not change the risk of contamination in the blood supply, nor improve results disclosure and referral to care.

Blood Donor Test-Seeking Motivation and Prior HIV Testing Experiences in São Paulo, Brazil.

HIV test-seeking behavior among blood donors has been observed worldwide and may pose a threat to the safety of the blood supply. We evaluated current test-seeking motivations and prior alternative HIV testing experiences among blood donors in São Paulo, Brazil. All candidate or potential blood donors were consecutively approached and recruited to participate in the study upon presentation at Fundação Pró-Sangue Hemocentro, the largest blood bank in Brazil. Participants were recruited between August 2012 and May 2013 after they were screened for donor eligibility. Questionnaires were administered through audio computer-assisted self-interview. Among 11,867 donors, 38 % previously tested for HIV apart from blood donation, of whom 47.7 % tested at public facilities and 2.7 % acknowledged getting tested for HIV as the primary reason for donating. Dissatisfaction with prior alternative testing experience was reported by 2.5 % of donors. Current test-seeking motivation was associated with dissatisfaction with prior alternative testing experience and testing at a public alternative facility. The most common reasons for dissatisfaction were too long of a wait to get tested and for results, counseling was too long, lack of privacy, and low confidence in the equipment and accuracy of the test. Lack of awareness about the availability of free and confidential public HIV testing services as well as dissatisfaction with past HIV testing and counseling experiences motivate some individuals to test at blood banks. Test-seeking behavior among blood donors may be best addressed by improving alternative testing programs, particularly with respect to time delays, privacy and perceptions about test accuracy. Educational campaigns on safe blood donation and HIV testing for diagnosis, risk counseling and referral to care are also needed for the general public and for health care providers.

Prevalence of serologic markers for hepatitis B and C viruses in Brazilian blood donors and incidence and residual risk of transfusion transmission of hepatitis C virus.

BACKGROUND: We evaluate the current prevalence of serologic markers for hepatitis B virus (HBV) and hepatitis C virus (HCV) in blood donors and estimated HCV incidence and residual transfusion-transmitted risk at three large Brazilian blood centers. STUDY DESIGN AND METHODS: Data on whole blood and platelet donations were collected from January through December 2007, analyzed by center; donor type; age; sex; donation status; and serologic results for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), and anti-HCV. HBV and HCV prevalence rates were calculated for all first-time donations. HCV incidence was derived including interdonation intervals that preceded first repeat donations given during the study, and HCV residual risk was estimated for transfusions derived from repeat donors. RESULTS: There were 307,354 donations in 2007. Overall prevalence of concordant HBsAg and anti-HBc reactivity was 289 per 100,000 donations and of anti-HCV confirmed reactivity 191 per 100,000 donations. There were significant associations between older age and hepatitis markers, especially for HCV. HCV incidence was 3.11 (95% confidence interval, 0.77-7.03) per 100,000 person-years, and residual risk of HCV window-phase infections was estimated at 5.0 per million units transfused. CONCLUSION: Improvement in donor selection, socioeconomic conditions, and preventive measures, implemented over time, may have helped to decrease prevalence of HBV and HCV, relative to previous reports. Incidence and residual risk of HCV are also diminishing. Ongoing monitoring of HBV and HCV markers among Brazilian blood donors should help guide improved recruitment procedures, donor selection, laboratory screening, and counseling strategies.

Human immunodeficiency virus prevalence, incidence, and residual risk of transmission by transfusions at Retrovirus Epidemiology Donor Study-II blood centers in Brazil.

BACKGROUND: In Brazil nationally representative donor data are limited on human immunodeficiency virus (HIV) prevalence, incidence, and residual transfusion risk. The objective of this study was to analyze HIV data obtained over 24 months by the Retrovirus Epidemiology Donor Study-II program in Brazil. STUDY DESIGN AND METHODS: Donations reactive to third- and fourth-generation immunoassays (IAs) were further confirmed by a less-sensitive (LS) IA algorithm and Western blot (WB). Incidence was calculated for first-time (FT) donors using the LS-EIA results and for repeat donors with a model developed to include all donors with a previous negative donation. Residual risk was projected by multiplying composite FT and repeat donor incidence rates by HIV marker-negative infectious window periods. RESULTS: HIV prevalence among FT donors was 92.2/10(5) donations. FT and repeat donor and composite incidences were 38.5 (95% confidence interval [CI], 25.6-51.4), 22.5 (95% CI, 17.6-28.0), and 27.5 (95% CI, 22.0-33.0) per 100,000 person-years, respectively. Male and community donors had higher prevalence and incidence rates than female and replacement donors. The estimated residual risk of HIV transfusion transmission was 11.3 per 10(6) donations (95% CI, 8.4-14.2), which could be reduced to 4.2 per 10(6) donations (95% CI, 3.2-5.2) by use of individual-donation nucleic acid testing (NAT). CONCLUSION: The incidence and residual transfusion risk of HIV infection are relatively high in Brazil. Implementation of NAT will not be sufficient to decrease transmission rates to levels seen in the United States or Europe; therefore, other measures focused on decreasing donations by at-risk individuals are also necessary.

Transfusion-Acquired HIV: History, Evolution of Screening Tests, and Current Challenges of Unreported Antiretroviral Drug Use in Brazil.

Prevention of HIV acquisition by blood transfusion from its emergence to the present day is reviewed, and current challenges are delineated. The experience of Fundação Pró-Sangue/Hemocentro de São Paulo, Brazil, is highlighted in the quest for improvements in blood safety and the evolution of increasingly sensitive and specific screening tests. Concerns and establishing stringent criteria in the screening of potential blood donors are emphasized, and the current criteria for identifying and deferring candidates at high risk of acquiring sexually transmitted diseases are summarized. Future challenges relate to the identification of donors with unreported use of antiretroviral drugs for prophylaxis against possible HIV exposure or for treatment of an HIV infection whose viral expression is undetectable by current analyses. There is a need to better understand the motivation of HIV-exposed donors and to educate them about the risk of transfusion-mediated HIV transmission despite having low or undetectable viral loads. In situations in which traditional HIV RNA or antibody detection assays remain negative, more sensitive analyses are needed to identify potential donors at risk for HIV transmission.

Predicting SARS-CoV-2 Variant Spread in a Completely Seropositive Population Using Semi-Quantitative Antibody Measurements in Blood Donors.

SARS-CoV-2 serologic surveys estimate the proportion of the population with antibodies against historical variants, which nears 100% in many settings. New approaches are required to fully exploit serosurvey data. Using a SARS-CoV-2 anti-Spike (S) protein chemiluminescent microparticle assay, we attained a semi-quantitative measurement of population IgG titers in serial cross-sectional monthly samples of blood donations across seven Brazilian state capitals (March 2021−November 2021). Using an ecological analysis, we assessed the contributions of prior attack rate and vaccination to antibody titer. We compared anti-S titer across the seven cities during the growth phase of the Delta variant and used this to predict the resulting age-standardized incidence of severe COVID-19 cases. We tested ~780 samples per month, per location. Seroprevalence rose to >95% across all seven capitals by November 2021. Driven by vaccination, mean antibody titer increased 16-fold over the study, with the greatest increases occurring in cities with the highest prior attack rates. Mean anti-S IgG was strongly correlated (adjusted R2 = 0.89) with the number of severe cases caused by Delta. Semi-quantitative anti-S antibody titers are informative about prior exposure and vaccination coverage and may also indicate the potential impact of future SARS-CoV-2 variants.

SARS-CoV-2 antibody dynamics in blood donors and COVID-19 epidemiology in eight Brazilian state capitals: A serial cross-sectional study.

Background: The COVID-19 situation in Brazil is complex due to large differences in the shape and size of regional epidemics. Understanding these patterns is crucial to understand future outbreaks of SARS-CoV-2 or other respiratory pathogens in the country. Methods: We tested 97,950 blood donation samples for IgG antibodies from March 2020 to March 2021 in 8 of Brazil's most populous cities. Residential postal codes were used to obtain representative samples. Weekly age- and sex-specific seroprevalence were estimated by correcting the crude seroprevalence by test sensitivity, specificity, and antibody waning. Results: The inferred attack rate of SARS-CoV-2 in December 2020, before the Gamma variant of concern (VOC) was dominant, ranged from 19.3% (95% credible interval [CrI] 17.5-21.2%) in Curitiba to 75.0% (95% CrI 70.8-80.3%) in Manaus. Seroprevalence was consistently smaller in women and donors older than 55 years. The age-specific infection fatality rate (IFR) differed between cities and consistently increased with age. The infection hospitalisation rate increased significantly during the Gamma-dominated second wave in Manaus, suggesting increased morbidity of the Gamma VOC compared to previous variants circulating in Manaus. The higher disease penetrance associated with the health system's collapse increased the overall IFR by a minimum factor of 2.91 (95% CrI 2.43-3.53). Conclusions: These results highlight the utility of blood donor serosurveillance to track epidemic maturity and demonstrate demographic and spatial heterogeneity in SARS-CoV-2 spread. Funding: This work was supported by Itaú Unibanco 'Todos pela Saude' program; FAPESP (grants 18/14389-0, 2019/21585-0); Wellcome Trust and Royal Society Sir Henry Dale Fellowship 204311/Z/16/Z; the Gates Foundation (INV- 034540 and INV-034652); REDS-IV-P (grant HHSN268201100007I); the UK Medical Research Council (MR/S0195/1, MR/V038109/1); CAPES; CNPq (304714/2018-6); Fundação Faculdade de Medicina; Programa Inova Fiocruz-CE/Funcap - Edital 01/2020 Number: FIO-0167-00065.01.00/20 SPU N°06531047/2020; JBS - Fazer o bem faz bem.

Performance of parallel screening of Brazilian blood donors with two human immunodeficiency virus immunoassays: implications for sequential immunoassay testing algorithms in other countries.

BACKGROUND: In Brazil it is mandatory to screen donors for human immunodeficiency virus (HIV) antibodies using two immunoassays (IAs) in parallel. Confirmatory testing is performed only on reactive donors who return for counseling. The goal of this analysis was to determine if concordant IA reactivity accurately predicts infection and can be used for HIV incidence and/or prevalence analyses. STUDY DESIGN AND METHODS: We reviewed HIV screening and confirmatory results obtained for 307,407 donations in the first year of the REDS-II study in Brazil (2007) and for 2,304,755 donations collected from 1996 to 2006 in one of the REDS-II sites (São Paulo, Brazil). RESULTS: In the São Paulo site, 11,410 (0.50%) HIV IA-reactive donations were discarded, but only 2095 (0.09%) were reactive to both IAs. Western blot was positive on 1002 (48%) dual-IA-reactive donors who returned for counseling. Only four HIV-infected donors were detected who had been missed at screening by one of the IAs; all occurred before 2002. The positive predictive value (PPV) of dual-IA reactivity varied from 45.8 to 100%, with 80% to 90% PPVs when using IAs from different manufacturers. If both assays yielded signal-to-cutoff (S/C) values of 3.0 or more, PPVs ranged from 91% to 99%, with approximately 99% sensitivity for true HIV seropositivity. CONCLUSION: Parallel testing of all donations has limited efficacy when highly sensitive IAs are used. Reactivity by two sequential IAs is useful for prevalence studies if the assays are from different manufacturers and especially if high S/C values are considered.