Due to the low sensitivity and reproducibility of available tests, in 1989 it became mandatory fo... more Due to the low sensitivity and reproducibility of available tests, in 1989 it became mandatory for all Brazilian blood donors to be screened for Chagas' disease by at least two serological techniques. In 1994 the Brazilian Ministry of health launched a program to systematically evaluate the quality of serological screening for the detection of blood-transmissible diseases as performed by public blood banks. A blind panel containing positive samples for blood-transmissible disease was distributed to 57 major public blood banks in four sequential programs. The ELISA test was chosen by the majority of the blood banks. There were 64 (3.7%) false-negative results, 49 produced by banks using indirect hemagglutination. Since most blood banks screened with more than one test for Chagas, only 8 samples were actually missed, of which 3 were by banks using only one test. Our data show a clear improvement in performance of Brazilian blood banks testing for Chagas' disease.
BACKGROUND: Concerted efforts have been directed toward recruitment of community rather than rep... more BACKGROUND: Concerted efforts have been directed toward recruitment of community rather than replacement donors in Brazil. Time trends and demographic correlates of human immunodeficiency (HIV) prevalence and incidence among first-time (FT) donors in Brazil were examined by donation type. HIV residual risk from FT-donor transfusions, and projected yield of p24 antigen and nucleic acid test (NAT) screening were estimated.STUDY DESIGN AND METHODS: HIV prevalence data and seroreactive specimens were obtained at Fundação Pró-Sangue/Hemocentro-de-São Paulo from 1995 to 2001. To estimate incidence, confirmed-positive samples from July 1998 through December 2001 were tested with a less-sensitive (detuned) enzyme immunoassay to detect recent seroconversions. Incidence data were used to estimate residual risk and p24 and NAT yield based on published window periods (WPs).RESULTS: HIV prevalence was 22 percent higher among the FT community donors than replacement donors (19.6 vs. 16.1 per 10,000; p < 0.01) and 48 percent higher among men than women (19.1 vs. 12.9; p < 0.01). In the multivariable logistic regression, both variables remained significant predictors of HIV prevalence. HIV prevalence decreased from 20.4 (1995) to 13.1 per 10,000 FT donations (2001). HIV incidence was 2.7 per 10,000 person-years. The estimated rate of infected antibody-negative donations was 14.9 per 1,000,000 units (95% confidence interval, 9.8-20.0). It was estimated that addition of p24 antigen, minipool NAT, and individual-donation NAT assays would detect 3.9 (2.0-5.8), 8.3 (5.3-11.3), and 10.8 (7.1-14.5) WP units per 1,000,000 FT donations, respectively.CONCLUSION: HIV incidence and residual transfusion risk estimates are approximately 10 times higher in Brazil FT donors compared to US and European FT donors. Community FT donors had higher HIV prevalence than replacement FT donors. The yield of p24 antigen or RNA screening will be low in Brazilian donors, but substantially higher than in US donors.
Jaids-journal of Acquired Immune Deficiency Syndromes, 2006
We analyzed rates of drug resistance mutations in antiretroviral-naive São Paulo blood donors wit... more We analyzed rates of drug resistance mutations in antiretroviral-naive São Paulo blood donors with recently acquired or established HIV-1 infections and characterized clade diversity in this population. Six hundred forty-eight seropositive blood donor specimens were identified at the Blood Center of São Paulo between July 1998 and March 2002. To discriminate recent infections, samples were subjected to the standardized testing algorithm for recent HIV seroconversion (less-sensitive enzyme immunoassay) testing algorithm. There were 531 samples with a sufficient volume of serum to attempt polymerase chain reaction (PCR) and viral sequencing; 341 (64%) samples yielded a PCR product that could be sequenced for the reverse transcriptase and protease genes. Mutations were analyzed using the 2005 International AIDS Society mutation list. Of 341 specimens successfully analyzed, 21 (6.3%; 95% confidence interval [CI]: 3.9% to 9.3%) had drug-resistant mutations. The proportion of resistant strains was 12.7% (95% CI: 5.2% to 24.5%) among recently infected individuals compared with 5.0% (95% CI: 2.8% to 8.2%) among those with long-standing infections (P = 0.03). No change in the proportion of drug-resistant strains was observed among recently infected donor samples from the first half of the study period (4 of 32 samples) as compared with the second half (3 of 23 samples; P = 0.95). Of the 341 samples, 277 (81.2%) were classified as subtype B, 25 (7.3%) as subtype F1, 13 (3.8%) as subtype C, and 26 (7.6%) as recombinant strains. The distribution of HIV-1 subtypes was similar among recent and long-standing infected individuals and over time. The prevalence of drug-resistant mutations among newly diagnosed persons in São Paulo city is low and similar to what has been described in Europe and the United States. Although HIV-1 subtype B remains predominant, subtypes F and C and recombinant forms are present in substantial proportions in infected donors.
To determine whether the HIV-1 genomes that grow out in vitro from peripheral blood mononuclear c... more To determine whether the HIV-1 genomes that grow out in vitro from peripheral blood mononuclear cells (PBMC) better represent the in vivo quasi-species present in plasma or PBMC. For one patient (9606), PBMC culture represented more accurately the plasma rather than the in vivo PBMC quasi-species distribution, because a large number of tat-defective proviruses present in PBMC in vivo were not detected in plasma nor in the PBMC cultures. For a second patient (9605), PBMC culture was representative of both in vivo PBMC and plasma tat sequences, but selection of C2-V3 env sequences was observed in PBMC cultures compared with sequences present in both plasma and PBMC in vivo. This selection consisted of the absence in vitro of genomes with certain amino-acid substitutions at or near conserved glycosylation sites of the C2 region at positions 276 and 289. Site 276 has been reported to be important for viral infectivity, and these substitutions may therefore have affected infectivity. In the third patient (10095), selection of both tat and C2-V3 sequences was observed in culture as compared to plasma and PBMC in vivo. In contrast to the first two patients, this third patient contained V3 sequences in vivo that were predicted to impart syncytium induction and enhanced replication capacity. It was these sequences that grew out preferentially in vitro. This study suggests that short-term PBMC culture is representative of HIV-1 genomes present in PBMC and plasma in vivo to the degree that they are infectious.
Revista panamericana de salud pública = Pan American journal of public health
In 1998, the Brazilian Ministry of Health made it mandatory for all blood banks in the country to... more In 1998, the Brazilian Ministry of Health made it mandatory for all blood banks in the country to screen donated blood for human immunodeficiency virus (HIV) concomitantly using two different enzyme immunoassay (EIA) tests. Concerned with the best use of available resources, our objective with this study was to evaluate the usefulness of conducting two EIA screening tests instead of just one. We analyzed data from 1999 through 2001 obtained by testing 698 191 units of donated blood using two EIA HIV screening tests concomitantly at the Pro-Blood Foundation/Blood Center of São Paulo (Fundação Pró-Sangue/Hemocentro de São Paulo), which is a major blood center in the city of São Paulo, Brazil. All samples reactive in at least one of the two EIA tests were submitted for confirmation by a Western blot (WB) test, and the persons who had donated those samples were also asked to return and provide a follow-up sample. Out of the 698 191 blood units that were donated, 2 718 of them (0.4%) had to be discarded because they were reactive to at least one of the EIA tests. There were two WB-positive donation samples that were reactive in only one HIV EIA screening test. On their follow-up samples, both donors tested WB-negative. These cases were considered false positive results at screening. Of the 2 718 donors who were asked to return and provide a follow-up sample, 1 576 of them (58%) did so. From these 1 576 persons, we found that there were two individuals who had been reactive to only one of the two EIA screening tests and who had also been negative on the WB at screening but who were fully seroconverted on the follow-up sample. We thus estimated that, in comparison to the use of a single EIA screening test, the use of two EIA screening tests would detect only one extra sample out of 410 700 units of blood. Our data do not support the use of two different, concomitant EIA screening tests for HIV. The great majority of HIV-positive donors have already seroconverted and will be detected using only a single EIA screening test. Only persons who are going through the process of seroconversion may be missed by using a single EIA test and detected using two EIAs for screening. To screen out these individuals and decrease the residual risk of HIV transmission from the blood donated in our center, the use of other techniques, such as nucleic acid testing (NAT) or a p24 antigen assay, would be more effective.
Background and Objective Previous studies have shown that volunteer, community-recruited donors ... more Background and Objective Previous studies have shown that volunteer, community-recruited donors have a higher prevalence of human immunodeficiency virus (HIV) infection in São Paulo, Brazil, than replacement donors. One hypothesis which may explain this unexpected finding is that some individuals donate blood because they are seeking HIV testing. The objective of this study was to characterize test-seeking blood donors and to determine whether they are at higher risk for HIV infection compared with other donors.Materials and Methods Subjects presenting for blood donation were asked to participate in a study assessing their motivations (including test seeking) to donate, as measured by perceiving donation as a means to obtain infectious disease test results. Participants completed the standard blood bank predonation screening questions plus our additional survey, and were tested for HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell lymphocytotrophic virus (HTLV) I/II, syphilis and Chagas’ disease. As a result of anticipated low statistical power to directly measure the association between test-seeking motivation and HIV infection, we tested for herpes simplex virus type 2 (HSV-2) as a marker of sexual risk for HIV. Our survey includes accepted donors as well as persons whose risk-behaviour histories would result in their exclusion from donation according to routine screening procedures.Results Of 1720 potential blood donors randomly selected and approached, 1600 (93·0%) participated. Overall, 141 (8·8%) were classified as test seekers; 15·6% of these were HSV-2 positive. The proportion of test seekers was the same among community-recruited and replacement donors. Test seekers had a higher prevalence of HSV-2 [adjusted odds ratio (AOR) 1·66; 95% confidence interval (CI): 1·06–2·59] adjusting for age, gender and prior donation. The association was significant among community-recruited blood donors whose previous donation was more than 1 year ago (i.e. ‘lapsed donors’) (AOR 2·55; 95% CI: 1·20–5·44). Test seekers were not more likely to be rejected from blood donation as a result of health reasons, self-reported HIV risk-related behaviour, or by their own confidential unit exclusion. We found no difference in HSV-2 prevalence between persons accepted for donation (15·7%) and those rejected because of self-reported sexual risk (16·7%).Conclusions We did not detect a difference in the proportion of test seekers across different types of blood donors; however, we did detect an association between HSV-2 infection and test seeking, especially among community-recruited lapsed blood donors. Of note, questions on test-seeking behaviour detected donors with increased prevalence of HSV-2, but the self-reported sexual risk behaviours currently used for deferral criteria did not. Incentives to get tested at sites other than blood banks may decrease the residual risk of HIV in the blood supply.
BACKGROUND: Brazilian blood centers ask candidate blood donors about the number of sexual partner... more BACKGROUND: Brazilian blood centers ask candidate blood donors about the number of sexual partners in the past 12 months. Candidates who report a number over the limit are deferred. We studied the implications of this practice on blood safety.STUDY DESIGN AND METHODS: We analyzed demographic characteristics, number of heterosexual partners, and disease marker rates among 689,868 donations from three Brazilian centers between July 2007 and December 2009. Donors were grouped based on maximum number of partners allowed in the past 12 months for each center. Chi-square and logistic regression analysis were conducted to examine associations between demographic characteristics, number of sex partners, and individual and overall positive markers rates for human immunodeficiency virus (HIV), human T-lymphotropic virus Types 1 and 2, hepatitis B virus, hepatitis C virus, and syphilis.RESULTS: First-time, younger, and more educated donors were associated with a higher number of recent sexual partners, as was male sex in São Paulo and Recife (p < 0.001). Serologic markers for HIV and syphilis and overall were associated with multiple partners in São Paulo and Recife (p < 0.001), but not in Belo Horizonte (p = 0.05, p = 0.94, and p = 0.75, respectively). In logistic regression analysis, number of recent sexual partners was associated with positive serologic markers (adjusted odds ratio [AOR], 1.2-1.5), especially HIV (AOR, 1.9-4.4).CONCLUSIONS: Number of recent heterosexual partners was associated with HIV positivity and overall rates of serologic markers of sexually transmitted infections. The association was not consistent across centers, making it difficult to define the best cutoff value. These findings suggest the use of recent heterosexual contacts as a potentially important deferral criterion to improve blood safety in Brazil.
BACKGROUND: Syphilis screening of blood donors is a common practice worldwide, but very little is... more BACKGROUND: Syphilis screening of blood donors is a common practice worldwide, but very little is known about the meaning of a positive serologic test for syphilis in blood donors and the risk profile of these donors. The aim of this study was to determine the demographic characteristics and risk behaviors of blood donors with recent and past syphilis and their implications for blood bank testing and deferral strategies.STUDY DESIGN AND METHODS: Demographic characteristics, category of donation, number of previous donations, sexual behavior, and history of sexually transmitted diseases were reviewed comparing blood donors with recent and past syphilis from January 1, 1999, to December 31, 2003.RESULTS: A total of 2439 interviews were reviewed, including 2161 (88.6%) donors with past and 278 (11.4%) with recent syphilis infection. Factors associated with recent infection included younger age (≤20 years odds ratio [OR], 36.5; 95% confidence interval [CI], 15.8-84.1), two previous donations (OR, 2.7; 95% CI, 1.9-3.9), male-male sex (homosexual OR, 8.2; 95% CI, 3.2-20.8; and bisexual OR, 11.4; 95% CI, 3.6-36.3), two or more partners in the past 12 months (OR, 2.3; 95% CI, 1.3-4.0), symptoms for syphilis (OR, 4.5; 95% CI, 2.8-7.1), and human immunodeficiency virus (HIV) seropositivity (OR, 39.6; 95% CI, 4.6-339.8). Community donors were also associated with recent syphilis infection (OR, 1.5; 95% CI, 1.2-1.9) compared to replacement donors.CONCLUSION: Sexual history, including male-male sex and multiple partners, were strongly associated with recent syphilis infection, which in turn was strongly associated with HIV. Continuous and vigilant surveillance that includes assessing sexual history and other factors associated with syphilis are needed to guide blood safety policies.
BACKGROUND: In Brazil it is mandatory to screen donors for human immunodeficiency virus (HIV) ant... more 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.
BACKGROUND: This study evaluated demographic profiles and prevalence of serologic markers among d... more BACKGROUND: This study evaluated demographic profiles and prevalence of serologic markers among donors who used confidential unit exclusion (CUE) to assess the effectiveness of CUE and guide public policies regarding the use of CUE for enhancing safety versus jeopardizing the blood supply by dropping CUE.STUDY DESIGN AND METHODS: We conducted a cross-sectional analysis of whole blood donations at a large public blood center in São Paulo from July 2007 through June 2009, compared demographic data, and confirmed serologic results among donors who used and who have never used CUE (CUE never).RESULTS: There were 265,550 whole blood units collected from 181,418 donors from July 2007 through June 2009. A total of 9658 (3.6%) units were discarded, 2973 (1.1%) because CUE was used at the current donation (CUE now) and 6685 (2.5%) because CUE was used in the past (CUE past). The CUE rate was highest among donors with less than 8 years of education (odds ratio [OR], 2.78; 95% confidence interval [CI], 2.51-3.08). CUE now donations were associated with higher positive infectious disease marker rates than CUE never donations (OR, 1.41; CI, 1.13-1.77), whereas CUE past donations were not (OR, 1.04; CI, 0.75-1.45).CONCLUSION: The CUE process results in a high rate of unit discard. CUE use on an individual donation appears predictive of a high-risk marker-positive donation and, thus, appears to contribute modestly to blood safety. The policy of discarding units from donors who have previously CUE-positive donations does not improve safety and should be discontinued.
Revista panamericana de salud pública = Pan American journal of public health, 2006
The first description of the human T-lymphotropic virus type 1 (HTLV-1) was made in 1980, followe... more The first description of the human T-lymphotropic virus type 1 (HTLV-1) was made in 1980, followed closely by the discovery of HTLV-2, in 1982. Since then, the main characteristics of these viruses, commonly referred to as HTLV-1/2, have been thoroughly studied. Central and South America and the Caribbean are areas of high prevalence of HTLV-1 and HTVL-2 and have clusters of infected people. The major modes of transmission have been through sexual contact, blood, and mother to child via breast-feeding. HTLV-1 is associated with adult T-cell leukemia/lymphoma (ATL), HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and HTLV-associated uveitis as well as infectious dermatitis of children. More clarification is needed in the possible role of HTLV in rheumatologic, psychiatric, and infectious diseases. Since cures for ATL and HAM/TSP are lacking and no vaccine is available to prevent HTLV-1 and HTLV-2 transmission, these illnesses impose enormous social and financial costs on infected individuals, their families, and health care systems. For this reason, public health interventions aimed at counseling and educating high-risk individuals and populations are of vital importance. In the Americas this is especially important in the areas of high prevalence.
This study characterized HIV-1 among antiretroviral-naïve populations presenting recent infection... more This study characterized HIV-1 among antiretroviral-naïve populations presenting recent infection (RI) or long-standing infection (LSI). Sera collected from January 1999 to December 2001 at an anonymous HIV testing site in Santos, Brazil, were submitted to serologic testing algorithm for recent HIV seroconversion (STARHS). The STARHS methodology uses a combination of a sensitive and a less sensitive version of an anti-HIV enzyme immunoassay (EIA), and specimens found to be positive on the sensitive EIA and negative on the less sensitive EIA are considered to represent RI. HIV-1 V3 and pol regions of those with RI and LSI were compared. Antiretroviral resistance was defined solely by genotypic analysis. Ninety samples were evaluated representing those taken from an original cohort of 345 individuals, for whom adequate samples were available. Of 90 HIV-positive individuals, 25 presented RI. Cumulatively, 36.8% of those with RI and 25% of those with LSI presented resistance to at least one antiretroviral class. In the pol and V3 regions, 47% and 53% of those with RI presented clade B viruses and B/F recombinant viruses, respectively, whereas 56.2%, 41.7%, and 2.1% of those with LSI harbored clades B, B/F, and clade C viruses, respectively. Primary resistance and the prevalence of B/F recombinants was high in this population. Monitoring HIV-1 genetic diversity is important for developing vaccines and treatment strategies.
Brazilian journal of medical and biological research = Revista brasileira de pesquisas médicas e biológicas / Sociedade Brasileira de Biofísica ... [et al.], 2001
BACKGROUND: Evaluation of commercially available test kits for Chagas disease for use in blood ba... more BACKGROUND: Evaluation of commercially available test kits for Chagas disease for use in blood bank screening is difficult due to a lack of large and well-characterized specimen panels. This study presents a collaborative effort of Latin American blood centers and the World Health Organization (WHO) to establish such a panel.STUDY DESIGN: A total of 437 specimens, from 10 countries were collected and sent to the WHO Collaborating Center in São Paulo and used to evaluate 19 screening assays during 2001 through 2005. Specimens were assigned a positive or negative status based on concordant results in at least three of the four confirmatory assays (indirect immunofluorescence, Western blot, radioimmunoprecipitation assay, and recombinant immunoblot).RESULTS: Of the 437 specimens, 168 (39%) were characterized as positive, 262 (61%) were characterized as negative, and 7 (2%) were judged inconclusive and excluded from the analysis. Sensitivity and specificity varied considerably: 88 to 100 and 60 to 100 percent, respectively. Overall, enzyme immunoassays (EIAs) performed better than the other screening assays. Four EIAs had both parameters higher than 99 percent. Of the four confirmatory assays, only the RIPA gave a 100 percent agreement with the final serologic status of the specimens.CONCLUSION: The sensitivities and specificities of at least four of the commercially available EIAs for Chagas disease are probably high enough to justify their use for single-assay screening of blood donations. Our data suggest that the majority of commercially available indirect hemagglutination assays should not be used for blood donor screening and that the RIPA could be considered a gold standard for evaluating the performance of other assays.
Due to the low sensitivity and reproducibility of available tests, in 1989 it became mandatory fo... more Due to the low sensitivity and reproducibility of available tests, in 1989 it became mandatory for all Brazilian blood donors to be screened for Chagas&amp;amp;amp;amp;#39; disease by at least two serological techniques. In 1994 the Brazilian Ministry of health launched a program to systematically evaluate the quality of serological screening for the detection of blood-transmissible diseases as performed by public blood banks. A blind panel containing positive samples for blood-transmissible disease was distributed to 57 major public blood banks in four sequential programs. The ELISA test was chosen by the majority of the blood banks. There were 64 (3.7%) false-negative results, 49 produced by banks using indirect hemagglutination. Since most blood banks screened with more than one test for Chagas, only 8 samples were actually missed, of which 3 were by banks using only one test. Our data show a clear improvement in performance of Brazilian blood banks testing for Chagas&amp;amp;amp;amp;#39; disease.
BACKGROUND: Concerted efforts have been directed toward recruitment of community rather than rep... more BACKGROUND: Concerted efforts have been directed toward recruitment of community rather than replacement donors in Brazil. Time trends and demographic correlates of human immunodeficiency (HIV) prevalence and incidence among first-time (FT) donors in Brazil were examined by donation type. HIV residual risk from FT-donor transfusions, and projected yield of p24 antigen and nucleic acid test (NAT) screening were estimated.STUDY DESIGN AND METHODS: HIV prevalence data and seroreactive specimens were obtained at Fundação Pró-Sangue/Hemocentro-de-São Paulo from 1995 to 2001. To estimate incidence, confirmed-positive samples from July 1998 through December 2001 were tested with a less-sensitive (detuned) enzyme immunoassay to detect recent seroconversions. Incidence data were used to estimate residual risk and p24 and NAT yield based on published window periods (WPs).RESULTS: HIV prevalence was 22 percent higher among the FT community donors than replacement donors (19.6 vs. 16.1 per 10,000; p < 0.01) and 48 percent higher among men than women (19.1 vs. 12.9; p < 0.01). In the multivariable logistic regression, both variables remained significant predictors of HIV prevalence. HIV prevalence decreased from 20.4 (1995) to 13.1 per 10,000 FT donations (2001). HIV incidence was 2.7 per 10,000 person-years. The estimated rate of infected antibody-negative donations was 14.9 per 1,000,000 units (95% confidence interval, 9.8-20.0). It was estimated that addition of p24 antigen, minipool NAT, and individual-donation NAT assays would detect 3.9 (2.0-5.8), 8.3 (5.3-11.3), and 10.8 (7.1-14.5) WP units per 1,000,000 FT donations, respectively.CONCLUSION: HIV incidence and residual transfusion risk estimates are approximately 10 times higher in Brazil FT donors compared to US and European FT donors. Community FT donors had higher HIV prevalence than replacement FT donors. The yield of p24 antigen or RNA screening will be low in Brazilian donors, but substantially higher than in US donors.
Jaids-journal of Acquired Immune Deficiency Syndromes, 2006
We analyzed rates of drug resistance mutations in antiretroviral-naive São Paulo blood donors wit... more We analyzed rates of drug resistance mutations in antiretroviral-naive São Paulo blood donors with recently acquired or established HIV-1 infections and characterized clade diversity in this population. Six hundred forty-eight seropositive blood donor specimens were identified at the Blood Center of São Paulo between July 1998 and March 2002. To discriminate recent infections, samples were subjected to the standardized testing algorithm for recent HIV seroconversion (less-sensitive enzyme immunoassay) testing algorithm. There were 531 samples with a sufficient volume of serum to attempt polymerase chain reaction (PCR) and viral sequencing; 341 (64%) samples yielded a PCR product that could be sequenced for the reverse transcriptase and protease genes. Mutations were analyzed using the 2005 International AIDS Society mutation list. Of 341 specimens successfully analyzed, 21 (6.3%; 95% confidence interval [CI]: 3.9% to 9.3%) had drug-resistant mutations. The proportion of resistant strains was 12.7% (95% CI: 5.2% to 24.5%) among recently infected individuals compared with 5.0% (95% CI: 2.8% to 8.2%) among those with long-standing infections (P = 0.03). No change in the proportion of drug-resistant strains was observed among recently infected donor samples from the first half of the study period (4 of 32 samples) as compared with the second half (3 of 23 samples; P = 0.95). Of the 341 samples, 277 (81.2%) were classified as subtype B, 25 (7.3%) as subtype F1, 13 (3.8%) as subtype C, and 26 (7.6%) as recombinant strains. The distribution of HIV-1 subtypes was similar among recent and long-standing infected individuals and over time. The prevalence of drug-resistant mutations among newly diagnosed persons in São Paulo city is low and similar to what has been described in Europe and the United States. Although HIV-1 subtype B remains predominant, subtypes F and C and recombinant forms are present in substantial proportions in infected donors.
To determine whether the HIV-1 genomes that grow out in vitro from peripheral blood mononuclear c... more To determine whether the HIV-1 genomes that grow out in vitro from peripheral blood mononuclear cells (PBMC) better represent the in vivo quasi-species present in plasma or PBMC. For one patient (9606), PBMC culture represented more accurately the plasma rather than the in vivo PBMC quasi-species distribution, because a large number of tat-defective proviruses present in PBMC in vivo were not detected in plasma nor in the PBMC cultures. For a second patient (9605), PBMC culture was representative of both in vivo PBMC and plasma tat sequences, but selection of C2-V3 env sequences was observed in PBMC cultures compared with sequences present in both plasma and PBMC in vivo. This selection consisted of the absence in vitro of genomes with certain amino-acid substitutions at or near conserved glycosylation sites of the C2 region at positions 276 and 289. Site 276 has been reported to be important for viral infectivity, and these substitutions may therefore have affected infectivity. In the third patient (10095), selection of both tat and C2-V3 sequences was observed in culture as compared to plasma and PBMC in vivo. In contrast to the first two patients, this third patient contained V3 sequences in vivo that were predicted to impart syncytium induction and enhanced replication capacity. It was these sequences that grew out preferentially in vitro. This study suggests that short-term PBMC culture is representative of HIV-1 genomes present in PBMC and plasma in vivo to the degree that they are infectious.
Revista panamericana de salud pública = Pan American journal of public health
In 1998, the Brazilian Ministry of Health made it mandatory for all blood banks in the country to... more In 1998, the Brazilian Ministry of Health made it mandatory for all blood banks in the country to screen donated blood for human immunodeficiency virus (HIV) concomitantly using two different enzyme immunoassay (EIA) tests. Concerned with the best use of available resources, our objective with this study was to evaluate the usefulness of conducting two EIA screening tests instead of just one. We analyzed data from 1999 through 2001 obtained by testing 698 191 units of donated blood using two EIA HIV screening tests concomitantly at the Pro-Blood Foundation/Blood Center of São Paulo (Fundação Pró-Sangue/Hemocentro de São Paulo), which is a major blood center in the city of São Paulo, Brazil. All samples reactive in at least one of the two EIA tests were submitted for confirmation by a Western blot (WB) test, and the persons who had donated those samples were also asked to return and provide a follow-up sample. Out of the 698 191 blood units that were donated, 2 718 of them (0.4%) had to be discarded because they were reactive to at least one of the EIA tests. There were two WB-positive donation samples that were reactive in only one HIV EIA screening test. On their follow-up samples, both donors tested WB-negative. These cases were considered false positive results at screening. Of the 2 718 donors who were asked to return and provide a follow-up sample, 1 576 of them (58%) did so. From these 1 576 persons, we found that there were two individuals who had been reactive to only one of the two EIA screening tests and who had also been negative on the WB at screening but who were fully seroconverted on the follow-up sample. We thus estimated that, in comparison to the use of a single EIA screening test, the use of two EIA screening tests would detect only one extra sample out of 410 700 units of blood. Our data do not support the use of two different, concomitant EIA screening tests for HIV. The great majority of HIV-positive donors have already seroconverted and will be detected using only a single EIA screening test. Only persons who are going through the process of seroconversion may be missed by using a single EIA test and detected using two EIAs for screening. To screen out these individuals and decrease the residual risk of HIV transmission from the blood donated in our center, the use of other techniques, such as nucleic acid testing (NAT) or a p24 antigen assay, would be more effective.
Background and Objective Previous studies have shown that volunteer, community-recruited donors ... more Background and Objective Previous studies have shown that volunteer, community-recruited donors have a higher prevalence of human immunodeficiency virus (HIV) infection in São Paulo, Brazil, than replacement donors. One hypothesis which may explain this unexpected finding is that some individuals donate blood because they are seeking HIV testing. The objective of this study was to characterize test-seeking blood donors and to determine whether they are at higher risk for HIV infection compared with other donors.Materials and Methods Subjects presenting for blood donation were asked to participate in a study assessing their motivations (including test seeking) to donate, as measured by perceiving donation as a means to obtain infectious disease test results. Participants completed the standard blood bank predonation screening questions plus our additional survey, and were tested for HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell lymphocytotrophic virus (HTLV) I/II, syphilis and Chagas’ disease. As a result of anticipated low statistical power to directly measure the association between test-seeking motivation and HIV infection, we tested for herpes simplex virus type 2 (HSV-2) as a marker of sexual risk for HIV. Our survey includes accepted donors as well as persons whose risk-behaviour histories would result in their exclusion from donation according to routine screening procedures.Results Of 1720 potential blood donors randomly selected and approached, 1600 (93·0%) participated. Overall, 141 (8·8%) were classified as test seekers; 15·6% of these were HSV-2 positive. The proportion of test seekers was the same among community-recruited and replacement donors. Test seekers had a higher prevalence of HSV-2 [adjusted odds ratio (AOR) 1·66; 95% confidence interval (CI): 1·06–2·59] adjusting for age, gender and prior donation. The association was significant among community-recruited blood donors whose previous donation was more than 1 year ago (i.e. ‘lapsed donors’) (AOR 2·55; 95% CI: 1·20–5·44). Test seekers were not more likely to be rejected from blood donation as a result of health reasons, self-reported HIV risk-related behaviour, or by their own confidential unit exclusion. We found no difference in HSV-2 prevalence between persons accepted for donation (15·7%) and those rejected because of self-reported sexual risk (16·7%).Conclusions We did not detect a difference in the proportion of test seekers across different types of blood donors; however, we did detect an association between HSV-2 infection and test seeking, especially among community-recruited lapsed blood donors. Of note, questions on test-seeking behaviour detected donors with increased prevalence of HSV-2, but the self-reported sexual risk behaviours currently used for deferral criteria did not. Incentives to get tested at sites other than blood banks may decrease the residual risk of HIV in the blood supply.
BACKGROUND: Brazilian blood centers ask candidate blood donors about the number of sexual partner... more BACKGROUND: Brazilian blood centers ask candidate blood donors about the number of sexual partners in the past 12 months. Candidates who report a number over the limit are deferred. We studied the implications of this practice on blood safety.STUDY DESIGN AND METHODS: We analyzed demographic characteristics, number of heterosexual partners, and disease marker rates among 689,868 donations from three Brazilian centers between July 2007 and December 2009. Donors were grouped based on maximum number of partners allowed in the past 12 months for each center. Chi-square and logistic regression analysis were conducted to examine associations between demographic characteristics, number of sex partners, and individual and overall positive markers rates for human immunodeficiency virus (HIV), human T-lymphotropic virus Types 1 and 2, hepatitis B virus, hepatitis C virus, and syphilis.RESULTS: First-time, younger, and more educated donors were associated with a higher number of recent sexual partners, as was male sex in São Paulo and Recife (p < 0.001). Serologic markers for HIV and syphilis and overall were associated with multiple partners in São Paulo and Recife (p < 0.001), but not in Belo Horizonte (p = 0.05, p = 0.94, and p = 0.75, respectively). In logistic regression analysis, number of recent sexual partners was associated with positive serologic markers (adjusted odds ratio [AOR], 1.2-1.5), especially HIV (AOR, 1.9-4.4).CONCLUSIONS: Number of recent heterosexual partners was associated with HIV positivity and overall rates of serologic markers of sexually transmitted infections. The association was not consistent across centers, making it difficult to define the best cutoff value. These findings suggest the use of recent heterosexual contacts as a potentially important deferral criterion to improve blood safety in Brazil.
BACKGROUND: Syphilis screening of blood donors is a common practice worldwide, but very little is... more BACKGROUND: Syphilis screening of blood donors is a common practice worldwide, but very little is known about the meaning of a positive serologic test for syphilis in blood donors and the risk profile of these donors. The aim of this study was to determine the demographic characteristics and risk behaviors of blood donors with recent and past syphilis and their implications for blood bank testing and deferral strategies.STUDY DESIGN AND METHODS: Demographic characteristics, category of donation, number of previous donations, sexual behavior, and history of sexually transmitted diseases were reviewed comparing blood donors with recent and past syphilis from January 1, 1999, to December 31, 2003.RESULTS: A total of 2439 interviews were reviewed, including 2161 (88.6%) donors with past and 278 (11.4%) with recent syphilis infection. Factors associated with recent infection included younger age (≤20 years odds ratio [OR], 36.5; 95% confidence interval [CI], 15.8-84.1), two previous donations (OR, 2.7; 95% CI, 1.9-3.9), male-male sex (homosexual OR, 8.2; 95% CI, 3.2-20.8; and bisexual OR, 11.4; 95% CI, 3.6-36.3), two or more partners in the past 12 months (OR, 2.3; 95% CI, 1.3-4.0), symptoms for syphilis (OR, 4.5; 95% CI, 2.8-7.1), and human immunodeficiency virus (HIV) seropositivity (OR, 39.6; 95% CI, 4.6-339.8). Community donors were also associated with recent syphilis infection (OR, 1.5; 95% CI, 1.2-1.9) compared to replacement donors.CONCLUSION: Sexual history, including male-male sex and multiple partners, were strongly associated with recent syphilis infection, which in turn was strongly associated with HIV. Continuous and vigilant surveillance that includes assessing sexual history and other factors associated with syphilis are needed to guide blood safety policies.
BACKGROUND: In Brazil it is mandatory to screen donors for human immunodeficiency virus (HIV) ant... more 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.
BACKGROUND: This study evaluated demographic profiles and prevalence of serologic markers among d... more BACKGROUND: This study evaluated demographic profiles and prevalence of serologic markers among donors who used confidential unit exclusion (CUE) to assess the effectiveness of CUE and guide public policies regarding the use of CUE for enhancing safety versus jeopardizing the blood supply by dropping CUE.STUDY DESIGN AND METHODS: We conducted a cross-sectional analysis of whole blood donations at a large public blood center in São Paulo from July 2007 through June 2009, compared demographic data, and confirmed serologic results among donors who used and who have never used CUE (CUE never).RESULTS: There were 265,550 whole blood units collected from 181,418 donors from July 2007 through June 2009. A total of 9658 (3.6%) units were discarded, 2973 (1.1%) because CUE was used at the current donation (CUE now) and 6685 (2.5%) because CUE was used in the past (CUE past). The CUE rate was highest among donors with less than 8 years of education (odds ratio [OR], 2.78; 95% confidence interval [CI], 2.51-3.08). CUE now donations were associated with higher positive infectious disease marker rates than CUE never donations (OR, 1.41; CI, 1.13-1.77), whereas CUE past donations were not (OR, 1.04; CI, 0.75-1.45).CONCLUSION: The CUE process results in a high rate of unit discard. CUE use on an individual donation appears predictive of a high-risk marker-positive donation and, thus, appears to contribute modestly to blood safety. The policy of discarding units from donors who have previously CUE-positive donations does not improve safety and should be discontinued.
Revista panamericana de salud pública = Pan American journal of public health, 2006
The first description of the human T-lymphotropic virus type 1 (HTLV-1) was made in 1980, followe... more The first description of the human T-lymphotropic virus type 1 (HTLV-1) was made in 1980, followed closely by the discovery of HTLV-2, in 1982. Since then, the main characteristics of these viruses, commonly referred to as HTLV-1/2, have been thoroughly studied. Central and South America and the Caribbean are areas of high prevalence of HTLV-1 and HTVL-2 and have clusters of infected people. The major modes of transmission have been through sexual contact, blood, and mother to child via breast-feeding. HTLV-1 is associated with adult T-cell leukemia/lymphoma (ATL), HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and HTLV-associated uveitis as well as infectious dermatitis of children. More clarification is needed in the possible role of HTLV in rheumatologic, psychiatric, and infectious diseases. Since cures for ATL and HAM/TSP are lacking and no vaccine is available to prevent HTLV-1 and HTLV-2 transmission, these illnesses impose enormous social and financial costs on infected individuals, their families, and health care systems. For this reason, public health interventions aimed at counseling and educating high-risk individuals and populations are of vital importance. In the Americas this is especially important in the areas of high prevalence.
This study characterized HIV-1 among antiretroviral-naïve populations presenting recent infection... more This study characterized HIV-1 among antiretroviral-naïve populations presenting recent infection (RI) or long-standing infection (LSI). Sera collected from January 1999 to December 2001 at an anonymous HIV testing site in Santos, Brazil, were submitted to serologic testing algorithm for recent HIV seroconversion (STARHS). The STARHS methodology uses a combination of a sensitive and a less sensitive version of an anti-HIV enzyme immunoassay (EIA), and specimens found to be positive on the sensitive EIA and negative on the less sensitive EIA are considered to represent RI. HIV-1 V3 and pol regions of those with RI and LSI were compared. Antiretroviral resistance was defined solely by genotypic analysis. Ninety samples were evaluated representing those taken from an original cohort of 345 individuals, for whom adequate samples were available. Of 90 HIV-positive individuals, 25 presented RI. Cumulatively, 36.8% of those with RI and 25% of those with LSI presented resistance to at least one antiretroviral class. In the pol and V3 regions, 47% and 53% of those with RI presented clade B viruses and B/F recombinant viruses, respectively, whereas 56.2%, 41.7%, and 2.1% of those with LSI harbored clades B, B/F, and clade C viruses, respectively. Primary resistance and the prevalence of B/F recombinants was high in this population. Monitoring HIV-1 genetic diversity is important for developing vaccines and treatment strategies.
Brazilian journal of medical and biological research = Revista brasileira de pesquisas médicas e biológicas / Sociedade Brasileira de Biofísica ... [et al.], 2001
BACKGROUND: Evaluation of commercially available test kits for Chagas disease for use in blood ba... more BACKGROUND: Evaluation of commercially available test kits for Chagas disease for use in blood bank screening is difficult due to a lack of large and well-characterized specimen panels. This study presents a collaborative effort of Latin American blood centers and the World Health Organization (WHO) to establish such a panel.STUDY DESIGN: A total of 437 specimens, from 10 countries were collected and sent to the WHO Collaborating Center in São Paulo and used to evaluate 19 screening assays during 2001 through 2005. Specimens were assigned a positive or negative status based on concordant results in at least three of the four confirmatory assays (indirect immunofluorescence, Western blot, radioimmunoprecipitation assay, and recombinant immunoblot).RESULTS: Of the 437 specimens, 168 (39%) were characterized as positive, 262 (61%) were characterized as negative, and 7 (2%) were judged inconclusive and excluded from the analysis. Sensitivity and specificity varied considerably: 88 to 100 and 60 to 100 percent, respectively. Overall, enzyme immunoassays (EIAs) performed better than the other screening assays. Four EIAs had both parameters higher than 99 percent. Of the four confirmatory assays, only the RIPA gave a 100 percent agreement with the final serologic status of the specimens.CONCLUSION: The sensitivities and specificities of at least four of the commercially available EIAs for Chagas disease are probably high enough to justify their use for single-assay screening of blood donations. Our data suggest that the majority of commercially available indirect hemagglutination assays should not be used for blood donor screening and that the RIPA could be considered a gold standard for evaluating the performance of other assays.
Screening of blood donors for Chagas&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;... more Screening of blood donors for Chagas&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; disease is mandatory in Brazil. Data about the prevalence of Chagas&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; disease among first-time blood donors has not been previously reported. The objective of this study was to report the trends in the prevalence of Chagas&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; disease among first-time blood donors in São Paulo, Brazil according to gender, age, and type of donation. The data was obtained at Fundação Pró-Sangue/Hemocentro de São Paulo during the period of 1996 to 2001. Samples were considered positive if they were reactive to the three serologic tests used at screening (indirect immunofluorescence, indirect hemagglutination, and EIA). The prevalence of Chagas&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; disease was two times higher among replacement blood donors than among altruistic donors (52 vs. 25 cases/10,000). The overall prevalence among blood donors decreased at a rate of 1.86 cases per 10,000 per year. An increase in the proportion of altruistic donors and a decrease in the prevalence primarily among younger donors were observed. The prevalence of Chagas&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; disease is decreasing in the São Paulo population. Differences in the socioeconomic level between altruistic and replacement donors may be the reason for the differences in the prevalence among these groups. It will be important to target for study the population of young seroreactive blood donors to better understand how new infections are occurring.
The presence of Treponema pallidum DNA was assessed by real-time PCR in samples of blood donors w... more The presence of Treponema pallidum DNA was assessed by real-time PCR in samples of blood donors with reactive serologic tests for syphilis. Treponema pallidum DNA was detected in two (1·02%) of 197 samples of VDRL&amp;amp;gt;8, EIA+ and FTA-ABS+ donors, and in no sample from 80 VDRL−, EIA+ and FTA-ABS+ donors. Donors VDRL−, EIA+ and FTA-ABS+ lack demonstrable T. pallidum DNA in their blood and are unlike to transmit syphilis. Donors VDRL&amp;amp;gt;8, EIA+ and FTA-ABS+ carry the risk of syphilis infectivity even in concomitance to antibodies detection. Serologic screening for syphilis may still play a role to prevent its transfusion transmission.
Background Chronic Chagas Cardiomyopathy (CCC) usually develops between 10 and 20 years after the... more Background Chronic Chagas Cardiomyopathy (CCC) usually develops between 10 and 20 years after the first parasitic infection and is one of the leading causes of end-stage heart failure in Latin America. Despite the great inter-individual variability in CCC susceptibility (only 30% of infected individuals ever present CCC), there are no known predictors for disease development in those chronically infected. Methodology/Principal findings We describe a new susceptibility locus for CCC through a GWAS analysis in the SaMi-Trop cohort, a population-based study conducted in a Chagas endemic region from Brazil. This locus was also associated with CCC in the REDS II Study. The newly identified locus (rs34238187, OR 0.73, p-value 2.03 x 10−9) spans a haplotype of approximately 30Kb on chromosome 18 (chr18: 5028302–5057621) and is also associated with 80 different traits, most of them blood protein traits significantly enriched for immune-related biological pathways. Hi-C data show that the ne...
INTRODUCTION Leg ulcers (LUs) are relatively common in patients with sickle cell anemia (SCA). Th... more INTRODUCTION Leg ulcers (LUs) are relatively common in patients with sickle cell anemia (SCA). The role of inflammation and nitric oxide (NO) pathways in the pathophysiology of the LU is not understood. OBJECTIVE The aim of this study was to verify the association between inflammatory molecules and nitric oxide metabolites (NOx) and the occurrence of the LU in patients with SCA. METHOD It was a cross-sectional study on adult participants with SCA followed at Fundação Hemominas, a public blood center in Brazil. Eligible participants were recruited and included in one of two groups: Group 1, comprised of cases with SCA (Hb SS) and at least one LU at the time of inclusion in the study and Group 2, comprised of controls with SCA without a history of LU, matched by sex and age to cases. Participants were interviewed to obtain sociodemographic data and blood samples were collected. Clinical and laboratory data were abstracted from medical records. Nitric oxide metabolites (NOx) and inflammatory molecules were quantified using an immunoassay and Multiplex xMAP® technology, respectively. Eighty-seven individuals were included, ranging in age from 17 to 61 years (mean 40 ± 10.7 years); 30 had LU and 57 were controls without LU. RESULTS Participants with LU had significantly higher levels of interleukin 8 (IL-8), IL-10, IL-15, NOx and platelet and white blood cell (WBC) counts, when compared to those without LU. Participants with LU had a significantly higher risk of having a history of osteomyelitis and a higher use of antiseptic soap in bathing, when compared to those without LU. CONCLUSION In conclusion, our results showed that NOx, inflammatory molecules and hematological features were associated with LU in Brazilian adults with SCA.
The efficacy of convalescent plasma (CP), an alternative for the treatment of COVID‐19, depends o... more 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.
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sabino e by Ester Sabino