Characterization of HIV risks in a Brazilian sickle cell disease population.

BACKGROUND: A low prevalence of HIV in sickle cell disease (SCD) patients has been reported in the literature though mechanisms for this are not understood. METHODS: HIV risk behaviors were compared between SCD cases and non-SCD controls using a self-administered audio computer-assisted self-interview. SCD cases were recruited from a multi-center SCD cohort established in Brazil; controls were recruited from SCD social contacts. Categorical variables were analyzed using Chi-Square or Fisher exact test. Continuous variables were compared using the Mann-Whitney U test. RESULTS: There were 152 SCD cases and 154 age/location matched controls enrolled at three participating Brazilian centers during 2016-17. No significant differences in number of sexual partners (lifetime or previous 12 months), male-to-male sex partners or intravenous drug use were observed. Cases received more transfusions, surgeries, and acupuncture treatment. CONCLUSIONS: Besides the risk of transfusion-transmitted HIV, which is now exceedingly rare, SCD and non-SCD participants demonstrated similar HIV risk behaviors. Causes other than risk behaviors such as factors inherent to SCD pathophysiology may explain the reported low prevalence of HIV in SCD.

Blood donation in a large urban centre of southeast Brazil: a population-based study.

OBJECTIVES: This study aimed to estimate the prevalence and characterise potential blood donors and non-donors in a well-populated and representative urban area of Southeastern Brazil. BACKGROUND: Studies on blood donation usually evaluate individuals who donate. Population-based studies may contribute to characterise those who never reach the blood centre, trying to increase the range of donors. STUDY DESIGN AND METHODS: This was a secondary analysis of a population-based survey and a blood donor motivation study [Recipient Epidemiology and Donor Evaluation study (REDS II) International]. In a cross-sectional study 4047 individuals representing a metropolitan area answered the question 'Have you ever donated blood at least once in your life?'. The profiles ('Yes/No') were compared. Non-donors from this reference population were compared with donors of a local blood center, in a case control analysis. RESULTS: A total of 69·0% of the population had never donated blood and was composed mostly of women, younger than 30 years old, people not contributing to social security and not subscribing to newspapers. In the case-control study, the likelihood of donating was higher for: men, younger than 50 years old, longer time of education, married, participating in political campaigns and with a good self-perception of health. The factors associated with no blood donation were: self-reported mixed or white race/ethnicity, income higher than two minimum wages and belonging to trade union, political, religious/spiritual, or other social group and worse self perception of health. CONCLUSIONS: This population-based study allowed us to characterise a high proportion of people that never reaches the blood centre. The results may be used to diversify the donor profile, creating strategies to target those least likely to donate blood, as women, white people and those with higher income and purchasing power.

Detection of Trypanosoma cruzi DNA in blood by PCR is associated with Chagas cardiomyopathy and disease severity.

BACKGROUND: The significance of detection of Trypanosoma cruzi DNA in blood of antibody-positive patients for risk of development of Chagas heart disease is not well established. The objective of this study was to compare detection of T. cruzi DNA with known clinical and laboratory markers of Chagas cardiomyopathy (CC) severity. METHODS: This is a case-control study nested within a retrospective cohort developed in Brazil to understand the natural history of Chagas disease. The study enrolled 499 T. cruzi seropositive blood donors (SP-BD) and 488 frequency matched seronegative control donors (SN-BD) who had donated between 1996 and 2002, and 101 patients with clinically diagnosed CC. In 2008-2010 all enrolled subjects underwent a health questionnaire, medical examination, electrocardiograms and echocardiograms and polymerase chain reaction (PCR) analyses. A blinded panel of three cardiologists adjudicated the outcome of CC. Trypanosoma cruzi kinetoplast minicircle sequences were amplified by real-time PCR using an assay with a sensitivity of one parasite per 20 mL of blood. All testing was performed on coded samples. RESULTS: Rates of PCR detection of T. cruzi DNA were significantly (P = 0.003) higher in CC patients and SP-BD diagnosed with CC (79/105 [75.2 %]) compared with SP-BD without CC (143/279 [51.3%]). The presence of parasitaemia was significantly associated with known markers of disease progression such as QRS and QT interval duration, lower left ventricular ejection fraction, higher left ventricular index mass, and elevated troponin and NTpro-BNP levels. CONCLUSION: Trypanosoma cruzi PCR positivity is associated with presence and severity of cardiomyopathy, suggesting a direct role of parasite persistence in disease pathogenesis.

Mother-to-Child Transmission of Human T-Cell Lymphotropic Viruses-1/2: What We Know, and What Are the Gaps in Understanding and Preventing This Route of Infection.

Although human T-cell lymphotropic viruses (HTLV-1/2) were described over 30 years ago, they are relatively unknown to the public and even to healthcare personnel. Although HTLV-1 is associated with severe illnesses, these occur in only approximately 10% of infected individuals, which may explain the lack of public knowledge about them. However, cohort studies are showing that a myriad of other disease manifestations may trouble infected individuals and cause higher expenditures with healthcare. Testing donated blood for HTLV-1/2 started soon after reliable tests were developed, but unfortunately testing is not available for women during prenatal care. Vertical transmission can occur before or after birth of the child. Before birth, it occurs transplacentally or by transfer of virus during cesarean delivery, but these routes of infection are rare. After childbirth, viral transmission occurs during breastfeeding and increases with longer breastfeeding and high maternal proviral load. Unlike the human immunodeficiency virus types 1 and 2, HTLV is transmitted primarily through breastfeeding and not transplacentally or during delivery. In this study, we review what is currently known about HTLV maternal transmission, its prevention, and the gaps still present in the understanding of this process.

Knowledge of HIV testing and attitudes towards blood donation at three blood centres in Brazil.

BACKGROUND: Reducing risk of HIV window period transmission requires understanding of donor knowledge and attitudes related to HIV and risk factors. STUDY DESIGN AND METHODS: We conducted a survey of 7635 presenting blood donors at three Brazilian blood centres from 15 October through 20 November 2009. Participants completed a questionnaire on HIV knowledge and attitudes about blood donation. Six questions about blood testing and HIV were evaluated using maximum likelihood chi-square and logistic regression. Test seeking was classified in non-overlapping categories according to answers to one direct and two indirect questions. RESULTS: Overall, respondents were male (64%) repeat donors (67%) between 18 and 49 years old (91%). Nearly 60% believed blood centres use better HIV tests than other places; however, 42% were unaware of the HIV window period. Approximately 50% believed it was appropriate to donate to be tested for HIV, but 67% said it was not acceptable to donate with risk factors even if blood is tested. Logistic regression found that less education, Hemope-Recife blood centre, replacement, potential and self-disclosed test-seeking were associated with less HIV knowledge. CONCLUSION: HIV knowledge related to blood safety remains low among Brazilian blood donors. A subset finds it appropriate to be tested at blood centres and may be unaware of the HIV window period. These donations may impose a significant risk to the safety of the blood supply. Decreasing test-seeking and changing beliefs about the appropriateness of individuals with behavioural risk factors donating blood could reduce the risk of transfusing an infectious unit.

Risk factors for human immunodeficiency virus infection among Brazilian blood donors: a multicentre case-control study using audio computer-assisted structured interviews.

BACKGROUND: Although risk factors for HIV infection are known, it is important for blood centres to understand local epidemiology and disease transmission patterns. Current risk factors for HIV infection in blood donors in Brazil were assessed. METHODS: A case-control study was conducted at large public blood centres located in four major cities between April 2009 and March 2011. Cases were persons whose donations were confirmed positive by enzyme immunoassays followed by Western blot confirmation. Audio computer-assisted structured interviews (ACASI) were completed by all cases and controls. Multivariable logistic regression was used to estimate adjusted odds ratios (AORs) and associated 95% confidence intervals (CIs). RESULTS: There were 341 cases, including 47 with recently acquired infection, and 791 controls. Disclosed risk factors for both females and males were sex with an HIV-positive person AOR 11.3, 95% CI (4.1, 31.7) and being an IVDU or sexual partner of an IVDU [AOR 4.65 (1.8, 11.7)]. For female blood donors, additional risk factors were having male sex partners who also are MSM [AOR 13.5 (3.1, 59.8)] and having unprotected sex with multiple sexual partners [AOR 5.19 (2.1, 12.9)]. The primary risk factor for male blood donors was MSM activity [AOR 21.6 (8.8, 52.9)]. Behaviours associated with recently acquired HIV were being a MSM or sex partner of MSM [13.82, (4.7, 40.3)] and IVDU [11.47, (3.0, 43.2)]. CONCLUSION: Risk factors in blood donors parallel those in the general population in Brazil. Identified risk factors suggest that donor compliance with selection procedures at the participating blood centres is inadequate.

Relationship between social capital and test seeking among blood donors in Brazil.

BACKGROUND AND OBJECTIVES: Higher risk of HIV infection could be associated with test seeking, which is one motivation for donating blood. Cognitive social capital is defined as the social support, trust and co-operation that guide community behaviour. Structural social capital refers to an individual's participation in institutions and organizations. The association between social capital and test seeking was assessed. MATERIALS AND METHODS: A survey of over 7500 donors in three Brazilian blood centres was conducted. Test seeking was classified into four non-overlapping categories (non-test seeker, possible, presumed and self-disclosed test seekers) using one direct and two indirect questions. Social capital was summarized into cognitive and structural categorizations. Multivariable logistic regression analysis was performed. RESULTS: Compared with non-test seekers (62% of survey respondents), cognitive social capital was higher for each category of test seeking (OR=1.1, 7.4, 7.1, P<0.05 respectively). Male gender, lower education and lower income were also significantly associated with test seeking. CONCLUSION: As test seekers appear to have strong social networks, blood banks may leverage this to convince them to seek testing at other locations.

Hierarchical analysis of anaemia deferral in blood donor candidates: the individual in the population perspective.

BACKGROUND AND OBJECTIVES: Deferral due to anaemia is common in blood donor selection, mainly owing to iron deficiency. This study analysed the prevalence of anaemia, its individual and group-associated factors in 335,095 blood donor candidates in the Hemominas Foundation, a public blood centre in Minas Gerais State, Brazil. MATERIALS AND METHODS: For the hierarchical analysis, gender, self-reported skin colour and age were included as independent variables at the individual level. Second level variables included proportion of self-reported white, male proportion, prevalence of sickle cell trait and Human Development Index (HDI) for the cities where the blood centres were located. RESULTS: Deferral due to anaemia was 9.71% in the donor population in the present study. Differences among geographic areas throughout the State were observed; living in an area with lower HDI (P < 0.032), female gender and non-white skin colour (both P < 0.001) were significantly associated with anaemia. Cities with a lower HDI had higher prevalence rates of anaemia when compared with the others. Anaemia was more pronounced among female and non-white donors and in the northern part of the State. CONCLUSION: A high deferral of blood donors due to anaemia, mostly associated with poverty was observed and deserves attention from the public health perspective. Blood centres should consider the profile of donors and their geographic location when planning mobile blood collection or regional campaigns.

Lookback study of HTLV-1 and 2 seropositive donors and their recipients in Belo Horizonte, Brazil.

The objective of this study was to perform lookback study in recipients of blood components from human T-lymphotropic virus (HTLV) seropositive donors. HTLV-1/2 may be transmitted by blood transfusion. Brazil is an endemic area for the virus and its screening in blood donors is mandatory since 1993. Hemominas Foundation (HF) is the public transfusion centre in Minas Gerais, Brazil. Data on HTLV-1/2 seropositive donors and recipients from 1993 to 2004 were obtained at HF and 24 contracting hospitals. From 1993 to 2004, HTLV-1/2 enzyme immunoassay (EIA) was performed in 918 678 donations of approximately 422 600 blood donor candidates. Of these, 456 donors (0.1%) were reactive and confirmed by Western blot (WB): 449 HTLV-1 and 7 HTLV-2. Sixty-six (14.5%) were repeat donors and had 194 blood cellular components produced from their previous donations. Of the distributed components, 119/146 (81.5%) had the recipient traced, with a total of 114 individuals. Of these, only 13 recipients were tested: six (46%) were HTLV-1 positive (four recipients of red cell units, two of platelets) and seven (54%) were negative (six of red cell units and one of platelets). Eleven did not respond and 62/114 (54.0%) were deceased. Another 28/114 (25.0%) could not be located. All six seropositive HTLV-1 recipients identified had no symptoms suggestive of HTLV-1-associated diseases. Acellular components, when used alone, were not associated with HTLV seropositivity. HTLV-1 transmission by cellular blood components occurred before screening for the virus was introduced. Haemovigilance was difficult to perform due to unavailability of computer systems before 1999 and to inadequate medical records at hospitals.

Transfusion-transmitted infectious diseases.

A spectrum of blood-borne infectious agents is transmitted through transfusion of infected blood donated by apparently healthy and asymptomatic blood donors. The diversity of infectious agents includes hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency viruses (HIV-1/2), human T-cell lymphotropic viruses (HTLV-I/II), Cytomegalovirus (CMV), Parvovirus B19, West Nile Virus (WNV), Dengue virus, trypanosomiasis, malaria, and variant CJD. Several strategies are implemented to reduce the risk of transmitting these infectious agents by donor exclusion for clinical history of risk factors, screening for the serological markers of infections, and nucleic acid testing (NAT) by viral gene amplification for direct and sensitive detection of the known infectious agents. Consequently, transfusions are safer now than ever before and we have learnt how to mitigate risks of emerging infectious diseases such as West Nile, Chikungunya, and Dengue viruses.

IL-10 produced by CD4+ and CD8+ T cells emerge as a putative immunoregulatory mechanism to counterbalance the monocyte-derived TNF-alpha and guarantee asymptomatic clinical status during chronic HTLV-I infection.

Although it is believed widely that distinct patterns of the host immune response are associated with the outcome of chronic human T cell lymphotropic virus type 1 (HTLV-I) infection toward asymptomatic or symptomatic neurodegenerative myelopathy (HAM/TSP), the exact mechanism underlying these immunological events still remains unknown. In this study, we have evaluated the cytokine pattern [interleukin (IL)-12, interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, IL-4 and IL-10] of innate and adaptive immunity cells present at the peripheral blood from non-infected (NI) and HTLV-I infected individuals [asymptomatic (AS), oligosymptomatic (OL) and HAM/TSP-HT], following in vitro short-term incubation in the absence/presence of phorbol myristate acetate (PMA) pan-leucocyte stimulation. In the absence of PMA stimulation, our data demonstrate that despite the overall immunological profile of AS mimicry that observed for NI, the high frequency of IL-12(+) neutrophils and TNF-alpha(+) monocytes are also a hallmark of this group of individuals. However, the outstanding positive correlation between the high frequency of TNF-alpha(+) monocytes and high levels CD4(+) IL-10(+) and CD8(+) IL-10(+) T cells suggests the establishment of immunoregulatory mechanisms that guarantee their asymptomatic clinical status. On the other hand, OL and HT did not present any association between the high frequency and TNF-alpha(+) neutrophils and monocytes and this immunoregulatory profile at their adaptive immunity cells. Upon PMA-index analysis, high levels of type 1 CD4(+) T cells, as well as higher IFN-gamma/IL-10 and TNF-alpha/IL-10 ratios, were observed in HT, and re-emphasize the role of Th1-cytokines from CD4(+) cells to HTLV-I immunity and disease. Moreover, increasing frequency of CD8(+) IFN-gamma(+) and CD8(+) TNF-alpha(+) cells were observed in the HT, which corroborates the marked inflammatory profile underlying this pathological condition and the role of CD8(+) T cells in the pathogenesis of HAM/TSP.

Establishing phenotypic features associated with morbidity in human T-cell lymphotropic virus type 1 infection.

The human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HT). Although it is widely believed that virus infection and host immune response are involved in the pathogenic mechanisms, the role of the immune system in the development and/or maintenance of HT remains unknown. We performed an analysis of the peripheral blood leukocyte phenotype for two different subcohorts of HTLV-1-infected individuals to verify the existence of similar immunological alterations, possible laboratory markers for HT. The leukocyte population balance, the activation status of the T lymphocytes, and the cellular migratory potential of T lymphocytes, monocytes, and neutrophils were evaluated in the peripheral blood of HTLV-1-infected individuals classified as asymptomatic individuals, oligosymptomatic individuals, and individuals with HT. Data analysis demonstrated that a decreased percentage of B cells, resulting in an increased T cell/B cell ratio and an increase in the CD8+ HLA-DR+ T lymphocytes, exclusively in the HT group could be identified in both subcohorts, suggesting its possible use as a potential immunological marker for HT for use in the laboratory. Moreover, analysis of likelihood ratios showed that if an HTLV-1-infected individual demonstrated B-cell percentages lower than 7.0%, a T cell/B cell ratio higher than 11, or a percentage of CD8+ HLA-DR+ T lymphocytes higher than 70.0%, this individual would have, respectively, a 12-, 13-, or 22-times-greater chance of belonging to the HT group. Based on these data, we propose that the T cell/B cell ratios and percentages of circulating B cells and activated CD8+ T lymphocytes in HTLV-1-infected patients are important immunological indicators which could help clinicians monitor HTLV-1 infection and differentiate the HT group from the asymptomatic and oligosymptomatic groups.

Phenotypic study of peripheral blood leucocytes in HTLV-I-infected individuals from Minas Gerais, Brazil.

The human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) associated with the HTLV-I is a well-defined clinical-pathological entity in which the virus and host immune responses contribute to the pathological mechanism. In this study, flow cytometric analysis of whole peripheral blood leucocytes (PBL) was performed to evaluate the immunological status of HTLV-I-infected individuals in an effort to better understand the role of the immune system in the development of HAM/TSP. We have evaluated three groups of infected patients including asymptomatic (AS = 18), ambulatory/oligosymptomatic (AM = 14) and hospitalized HAM/TSP individuals (HO = 42). Noninfected healthy blood donors were used for the control group (NI = 32). Our results demonstrated that the HO group presents an increased percentage of circulating T cells and a decreased percentage of B and natural killer (NK) cells, leading to the highest T/B-cell ratio in comparison with the other groups. Interestingly, while an increased percentage of activated CD4+HLA-DR+ T lymphocytes was observed in both AM and HO, only HO presented higher percentage of activated CD8+HLA-DR+ in combination with the highest CD18 surface expression. This was true for all cell populations analysed, including T lymphocytes, monocytes and neutrophils. Moreover, the HO group was distinguished by a dramatic decrease in the percentage of CD8+CD28+ lymphocytes. Taken together, these findings demonstrate a potent cellular immune activation response involving primarily CD8+ T cells that is concomitant with disease progression in HAM/TSP. We also show that an upregulation of CD18 expression, a hallmark for increased cell migratory potential, might play a critical role in the development/maintenance of HAM/TSP.

Prevalence of HIV-1/2, HTLV-I/II, hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum and Trypanosoma cruzi among prison inmates at Manhuaçu, Minas Gerais State, Brazil.

The purpose of this study was to determine the seroprevalence of human immunodeficiency virus (HIV-(1/2)), human T-cell lymphotropic virus (HTLV-I/II), hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum and Trypanosoma cruzi among 63 male prisoners in Manhuaçu, Minas Gerais, Brazil and to compare this with data from eligible blood donors. The positive results were as follows: 11/63 (17.5%) for HBV, 5/63 (7.4%) for syphilis, 4/63 (6.3%) for HCV, 3/63 (4.8%) for Chagas' disease, 2/63 (3.2%) for HIV-1/2 and 1/63 (1.6%) for HTLV-I/II. The seroprevalence in prisoners was higher than among blood donors, mainly for antibodies to HIV-1/2, HCV and HBV. This is probably due to low social economic level, illiteracy, higher proportion with a prior history of intravenous drug use and/or unsafe sexual behavior. Therefore, these prisoners constitute a high-risk group and routine screening and counseling are recommended.

HTLV-I associated infective dermatitis may be an indolent HTLV-I associated lymphoma.

When present for a first time blood donation, a 28-year-old Brazilian white female reported a pruritic eczema of the scalp and retroauricular areas since childhood that had been frequently infected. Her mother had been diagnosed as having HTLV-I-associated myelopathy (HAM), and the patient was found to be a human T-lymphotropic virus type-I (HTLV-I) carrier. The patient had been breast-fed for 6 months. The patient had a complete examination, and a biopsy was taken from eczema in the retroauricular area. The biopsy indicated chronic lymphohistiocytic dermatitis with no abnormal lymphocytes. Eleven months later, the patient had an infiltration in the skin of the retroauricular area and a new biopsy revealed atypical lymphocytes. Nested polymerase chain reaction (PCR) was positive for HTLV-I and immunohistochemistry of the tissue at this time confirmed adult T-cell leukemia/lymphoma (ATLL). Retrospective immunohistochemistry showed that the first fragment submitted from the biopsy 11 months before was also compatible with the diagnosis of ATLL. This case fulfilled all major criteria for diagnosis of HTLV-I-associated infective dermatitis (HTLV-I-ID). We postulate that the patient had indolent ATLL associated with HTLV-I infective dermatitis since childhood. We recommend that tissue immunohistochemistry analysis be done in any patient with HTLV-associated infective dermatitis.

HIV-1/2 indeterminate western blot results: follow-up of asymptomatic blood donors in Belo Horizonte, Minas Gerais, Brazil

A importancia clinica e de saude publica de resultados indeterminados em exames para HIV-1/2 e ainda dificil de avaliar em doadores de sangue voluntarios. Na Fundacao Hemominas e utilizado um teste de triagem (ELISA) que, se reativo, e seguido pelo Western blot (WB). Avaliamos nesse estudo 84 doadores que apresentavam ELISA repetidamente reativo, mas WB indeterminado. Dos 84 individuos, 16 (19 por cento) tinham historia de doencas sexualmente transmissiveis; 18/84 (21,4 por cento) informaram ter recebido ou pago por sexo; 3/84 (3,6 por cento) informaram contacto homosexual; 2/26 mulheres (7,6 por cento) tinham historia pregressa de multiplos abortos ilegais e 3/84 (3,6 por cento) tinham sidos transfundidos. Quatro de 62 doadores (6,5 por cento) tinham fator anti-nuclear (Hep2) positivo, com titulos de ate 1:640. Exame parasitologico revelou a presenca de ovos de S. mansoni nas fezes de 4/62 (6,4 por cento) e outros parasitas em 8/62 (12,9 por cento). Cinco individuos (5,9 por cento) apresentaram franca conversao para HIV-1/2 no WB; 43/84 (51,2 por cento) tinham resultados negativos na ultima visita, enquanto que 36/84 (42,9 por cento) permaneceram com o WB inderterminado. Concluimos que, embora pudessemos encontrar algumas condicoes associadas ao resultado inderminado para HIV-1/2 no WB e muitos doadores com historia pregressa de comportamento de risco, o significado da maioria dos resultados ainda necessita elucidacao

Erectile insufficiency as first symptom of HTLV I/II associated myelopathy. Case report.

A case of HTLV-I/II myelopathy in which the initial complaint was erectile insufficiency (EI) is reported. The only abnormalities found on the neurological exam were discrete weakness of the psoas and increased knee jerk reflexes. Diagnosis was made by demonstrating antibodies anti-HTLV I/II in the serum and cerebrospinal fluid (with the techniques of ELISA and Western blot), with confirmation by the polymerase chain reaction (PCR). EI can thus be the first symptom of HTLV-I/II infection and patients with EI of unknown etiology should be tested for HTLV-I/II in endemic areas.