RESUMO
The present study compares the ability of distinct immunological assays (chemiluminescence immunoassay-CLIA, western blot-WB and flow cytometry-FC-Simplex and Duplex) to detect anti-HTLV (human T-lymphotropic virus) antibodies in candidates for blood donations at the Amazonas State Blood Center (Brazil) between January 2018 and December 2022. Overall, 257,942 samples from candidates for blood donations were screened using CLIA, which led to 0.15% seropositivity for HTLV (409 samples). A total of 151 candidates for blood donations were enrolled for retesting with CLIA followed by additional testing using WB and FC-Simplex and Duplex analysis. Our results demonstrated that 62% (93/151), 20% (30/151) and 17% (26/151) of the samples presented positive results with retesting using CLIA, WB and FC-Simplex analysis, respectively. Additional analysis of the CLIA, WB and FC-Simplex results revealed an overall agreement of 56% for CLIA and WB (22 co-negative; 30 co-positive samples), 48% for CLIA and FC-Simplex (21 co-negative; 24 co-positive samples) and 80% for WB and FC-Simplex (51 co-negative; 23 co-positive samples). Considering the WB as the reference standard for the diagnosis of infection with HTLV-1/2, we observed that the CLIA results of ≤3.0 RLU and >10.0 RLU in the retest can be used define a negative or positive result, respectively, and could be used as new specific cut-off values. The overall agreement between WB and FC-Duplex for accomplishing the differential diagnosis was evaluated and demonstrated 100% correspondence for the diagnosis of HTLV-1 (15/15) and HTLV-2 (7/7). Our findings demonstrate that gaps in the diagnosis of infection with HTLV-1/2 could be overcome by the simultaneous use of distinct immunological assays during retesting of candidates for blood donations.
Assuntos
Doadores de Sangue , Infecções por HTLV-I , Infecções por HTLV-II , Vírus Linfotrópico T Tipo 1 Humano , Vírus Linfotrópico T Tipo 2 Humano , Humanos , Brasil , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-I/sangue , Infecções por HTLV-I/imunologia , Infecções por HTLV-II/diagnóstico , Infecções por HTLV-II/sangue , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Vírus Linfotrópico T Tipo 2 Humano/imunologia , Masculino , Feminino , Adulto , Diagnóstico Diferencial , Pessoa de Meia-Idade , Western Blotting , Citometria de Fluxo/métodos , Doação de SangueRESUMO
Human T-Lymphotropic Virus type-1 (HTLV-1) is a unique retrovirus associated with both leukemogenesis and a specific neuroinflammatory condition known as HTLV-1-Associated Myelopathy (HAM). Currently, most proposed HAM biomarkers require invasive CSF sampling, which is not suitable for large cohorts or repeated prospective screening. To identify non-invasive biomarkers for incident HAM in a large Brazilian cohort of PLwHTLV-1 (n=615 with 6,673 person-years of clinical follow-up), we selected all plasma samples available at the time of entry in the cohort (between 1997-2019), in which up to 43 cytokines/chemokines and immune mediators were measured. Thus, we selected 110 People Living with HTLV-1 (PLwHTLV-1), of which 68 were neurologically asymptomatic (AS) at baseline and 42 HAM patients. Nine incident HAM cases were identified among 68 AS during follow-up. Using multivariate logistic regression, we found that lower IL-10, IL-4 and female sex were independent predictors of clinical progression to definite HAM (AUROC 0.91), and outperformed previously suggested biomarkers age, sex and proviral load (AUROC 0.77). Moreover, baseline IL-10 significantly predicted proviral load dynamics at follow-up in all PLwHTLV-1. In an exploratory analysis, we identified additional plasma biomarkers which were able to discriminate iHAM from either AS (IL6Rα, IL-27) or HAM (IL-29/IFN-λ1, Osteopontin, and TNFR2). In conclusion, female sex and low anti-inflammatory IL-10 and IL-4 are independent risk factors for incident HAM in PLwHTLV-1,while proviral load is not, in agreement with IL-10 being upstream of proviral load dynamics. Additional candidate biomarkers IL-29/IL-6R/TNFR2 represent plausible therapeutic targets for future clinical trials in HAM patients.
Assuntos
Biomarcadores , Vírus Linfotrópico T Tipo 1 Humano , Interleucina-10 , Carga Viral , Humanos , Feminino , Masculino , Brasil/epidemiologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Interleucina-10/sangue , Biomarcadores/sangue , Pessoa de Meia-Idade , Adulto , Infecções por HTLV-I/imunologia , Infecções por HTLV-I/sangue , Infecções por HTLV-I/diagnóstico , Provírus , Estudos de Coortes , Paraparesia Espástica Tropical/sangue , Paraparesia Espástica Tropical/imunologia , Paraparesia Espástica Tropical/virologia , IncidênciaRESUMO
Infective dermatitis associated with human T-cell lymphotropic virus type-1 (HTLV-1) (IDH) is a severe form of chronically infected eczema occurring in early childhood, although very rarely cases have been reported in adults. Most of the cases are from Jamaica and Brazil and occur in individuals with low socioeconomic status. IDH is always associated with refractory Staphylococcus aureus or beta-hemolytic Streptococcus infection of the skin and nasal vestibules. Patients with IDH may develop other even more severe HTLV-1-associated diseases, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) of early or late appearance and adult T-cell leukemia/lymphoma. In the context of the Brazilian experience, it has been observed that 54% of IDH patients exhibit the juvenile form of HAM/TSP while the estimated incidence of adult HAM/TSP is 3%. As there are no curative treatments for HTLV-1 infection (or vaccines) or most of its associated diseases, prevention of infection is fundamental, mainly by vertical transmission, as it is responsible for the development of IDH, infantojuvenile HAM/TSP, and ATL. Public measures to reduce this transmission must be implemented urgently. Furthermore, it is recommended, mainly in HTLV-1 endemic areas, to search for HTLV-1 infection in all patients with infected eczema, even in adults.
Assuntos
Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Humanos , Infecções por HTLV-I/complicações , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-I/epidemiologia , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Brasil/epidemiologia , Paraparesia Espástica Tropical/diagnóstico , Paraparesia Espástica Tropical/virologia , Paraparesia Espástica Tropical/epidemiologia , Adulto , Dermatite/virologia , Dermatite/diagnósticoRESUMO
Introduction: Migratory flows play a significant role in the spread of human T-lymphotropic virus 1/2 (HTLV-1/2). In the last decade, a substantial migration of individuals occurred from Haiti and Venezuela to Brazil. However, data on the prevalence of HTLV-1/2 infection among these international migrants in Brazil are scarce. This study describes the prevalence of this infection among immigrants and refugees in Central Brazil. Methods: A cross-sectional study was conducted with 537 international migrants in the State of Goiás, Central Brazil. Participants were interviewed, and blood samples were collected. Serological screening for anti-HTLV-1/2 was performed using an enzyme-linked immunosorbent assay (ELISA; Murex HTLV-I + II, DiaSorin, Dartford, UK), and seropositive samples were submitted for confirmation by a line immunoassay (INNO-LIA HTLV I/II, Fujirebio, Europe N.V., Belgium). Results: The majority of participants were males (54.4%), between 18 and 50 years old (78%; mean age: 29.1 years), self-declared black (55.1%), reported 1 to 12 years of formal education (70.9%), and were either Venezuelans (47.9%) or Haitians (39.7%). Additionally, 50.1% were immigrants, 49% were refugees, and five were Brazilian children (0.9%) born to Haitian immigrant parents. The overall prevalence of anti-HTLV-1/2 was 0.95% (95% CI: 0.31-2.28), with HTLV-1 at 0.19% and HTLV-2 at 0.76%. All seropositive individuals (n = 5) were refugees from Venezuela, resulting in a rate of 2.26% for anti-HTLV-1/2, HTLV-1 (0.45%) and HTLV-2 (1.81%) among Venezuelan refugees. Of the demographic and behavioral characteristics evaluated, unprotected sexual intercourse and having more than one sexual partner (≥2) in the previous 12 months were associated with HTLV-1/2 seropositivity among Venezuelans. Conclusion: This study revealed, despite the low seroprevalence of HTLV-1/2 among international migrants in Central Brazil, evidence of HTLV-1 and HTLV-2 infections in Venezuelan refugees. In addition, their characteristics highlight that specific social and health programs should be implemented for these emergent and socially vulnerable migrant groups.
Assuntos
Emigrantes e Imigrantes , Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Refugiados , Masculino , Criança , Humanos , Adulto , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Feminino , Brasil/epidemiologia , Estudos Transversais , Estudos Soroepidemiológicos , Haiti , Populações Vulneráveis , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/diagnóstico , Vírus Linfotrópico T Tipo 2 HumanoRESUMO
Mother to child transmission (MTCT) of human T-cell lymphotropic virus (HTLV)-1 is associated with increased risk of adult T-cell leukemia and can be unrecognized without routine antenatal screening. We assessed the seroprevalence of HTLV-1/2 among pregnant women attending The University Hospital of the West Indies Antenatal Clinic, 2019, and validated a cost-effective strategy to screen antenatal clinic attendees for HTLV-1/2. Residual antenatal samples from 370 women were tested for HTLV-1/2 by chemiluminescence microparticle immunoassay (CMIA). Six samples were confirmed HTLV-1 positive by Western blot (none for HTLV-2) for a prevalence of 1.62%. Four mother-child pairs were able to be recruited for HTLV testing of children, with two children testing HTLV-1/2 positive. Medical records of HTLV-1-infected women revealed that all women breastfed, indicating an unrecognized risk for HTLV MTCT. To assess whether pooling of samples as a cost-reduction strategy could be introduced, we pooled all antenatal samples received between November and December 2021 into 12 pools of eight samples/pool. Two pools were CMIA positive, and de-pooling of samples identified two CMIA-positive samples (one per pool), both confirmed as HTLV-1 by Western blot. These results indicate that HTLV-1 remains prevalent in pregnant Jamaican women and that sample pooling can be a cost-effective strategy to limit MTCT in Jamaica.
Assuntos
Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Adulto , Feminino , Humanos , Gravidez , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/prevenção & controle , Estudos Soroepidemiológicos , Jamaica/epidemiologia , Transmissão Vertical de Doenças Infecciosas , Diagnóstico Pré-Natal , Linfócitos TRESUMO
INTRODUCTION: The present study had the objective to describe the molecular prevalence and epidemiological aspects of the human T-lymphotropic virus 2 (HTLV-2) infection in the blood donor population of the Pará state. METHODS: The present study is a descriptive, retrospective, and cross-sectional review of epidemiological, serological, and molecular data on inapt blood donors in the State Center for Hematology and Hemotherapy from January 2015 to December 2021. The data were digitalized to create a database using the Statistical Package for Social Sciences program. The prevalence of HTLV-2 was calculated based on the total number of donations during the study period. Descriptive frequency was used to analyze the qualitative data. RESULTS: A total of 665,568 blood donations were made. Out of these, 1884 (0.2%) samples presented serological detection to HTLV and further were evaluated using molecular confirmatory tests. Out of these, 36 samples were positive for HTLV-2 using qPCR Taqman assay based on pol gene region (0.005%). The HTLV-2 was found to be more prevalent in women (63.9%); aged between 39 and 59 years (55.6%); residents of the metropolitan region of Belém (80.6%); with self-declared race as brown (80.6%); individuals who had completed high school (58.6%); and first-time donors (58.3%) CONCLUSION: The present study identified the presence of HTLV-2 (1 HTLV-2 case/20,000 donations; 0.005%) in the specific population of blood donors in Pará state. These findings can contribute to the existing literature on the subject both for specific population groups under study and for understanding the prevalence of HTLV-2 in the general population.
Assuntos
Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Vírus Linfotrópico T Tipo 2 Humano/genética , Doadores de Sangue , Vírus Linfotrópico T Tipo 1 Humano/genética , Infecções por HTLV-I/diagnóstico , Prevalência , Brasil/epidemiologia , Estudos Transversais , Estudos RetrospectivosRESUMO
En el presente estudio describimos y caracterizamos la distribución geográfica de los casos positivos confirmados a HTLV-1 y 2 de pacientes peruanos con diagnóstico presuntivo entre 2019 y 2021. De un total de 555 muestras positivas confirmadas, 546 (98,4%) fueron HTLV-1 y 9 (1,6%) HTLV-2. Además, 22 de 24 departamentos del Perú presentaron casos de HTLV-1, siendo los principales motivos de solicitud de confirmación diagnóstica: aspirante a donar sangre con prueba de tamizaje reactivo, sospecha de leucemia/linfoma y paraparesia espástica tropical. Los resultados reflejan que la identificación de los puntos críticos constituye una brecha persistente respecto al diagnóstico, siendo cruciales para reducir el número de nuevos casos en Perú.
In the present study we describe and characterize the geographic distribution of HTLV-1 and 2 positive cases from Peruvian patients with presumptive diagnosis 2019 - 2021. Of a total of 555 confirmed positive samples, 546 (98.4%) were HTLV-1 and 9 (1.6%) HTLV-2. In addition, 22 of 24 departments of Peru presented cases of HTLV-1. The main reasons for requesting a confirmatory diagnosis being: aspiring to donate blood with a reactive screening test, suspicion of leukemia/ lymphoma and tropical spastic paraparesis. The results reflect that the identification of critical points constitutes a persistent gap regarding the diagnosis, being crucial to reduce the number of new cases in Peru.
Assuntos
Humanos , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-II/epidemiologia , Peru/epidemiologia , Vírus Linfotrópico T Tipo 1 Humano , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-II/diagnóstico , Leucemia-Linfoma de Células T do Adulto , Paraparesia Espástica Tropical , Estudos Transversais , GeografiaRESUMO
In 2012, the number of people infected with human T cell lymphotropic virus type 1 (HTLV-1) was estimated to be 10 million worldwide. Prevalence varies according to geographic location, ethnic factors, sex, age, populations exposed to risk factors, income, and education, reaching countries with the worst socioeconomic scenarios. There is a need to determine the current global prevalence of HTLV-1 and examine its association with countries' human development index (HDI) to provide data for global health policy. Systematic review with meta-analysis is according to PRISMA 2020 recommendations. It was registered at PROSPERO, CRD42021223146. Prevalence or cross-sectional studies of HTLV-1 infection with at least 100 participants, screening, and confirmatory serologic testing were included. Studies with incomplete or unavailable results or with duplicate information were excluded. Data were selected by two independent investigators and analyzed using R software, a metapackage that generated the forest plots [95% confidence interval (CI)]. Heterogeneity was assessed using the I2 statistic, and funnel plot asymmetry was assessed using Egger's test. Countries were compared using an HDI cutoff ≥0.8. Methodological quality was assessed using Joanna Briggs Institute (JBI) criteria. The overall prevalence of HTLV-1 infection was 0.91% (95% CI: 0.80-1.02, p < .0001) and was higher in low HDI countries [1.18% (95% CI: 1.03-1.34)] than in high HDI countries [0.41% (95% CI: 0.27-0.57)]. Prevalence varied according to the populations studied: it was higher in the general population [1.65% (95% CI: 1.08-2.34)] compared to pregnant women [0.34% (95% CI: 0.17-0.57)] and blood donors [0.04% (95% CI: 0.01-0.08)]. Consistently, prevalence for each population group was higher in low HDI countries than in high HDI countries. The worldwide prevalence of HTLV-1 infection is highly heterogeneous, with a global prevalence of 0.91%. In high HDI countries, the observed prevalence is approximately three times lower than in low HDI countries. In the general population, the observed prevalence is about 5 times higher than in pregnant women and 41 times higher than in blood donors.
Assuntos
Infecções por HIV , Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Humanos , Feminino , Gravidez , Prevalência , Estudos Transversais , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/diagnóstico , Linfócitos TRESUMO
Human T-lymphotropic viruses 1 and 2 (HTLV-1 and HTLV-2) infection has been described in several Amazonian populations; however, there is still a lack of data on the prevalence of the virus in riparian populations living in rural areas of the state of Pará. The present study aimed to evaluate the prevalence of HTLV-1/2 infection in four riverine communities and one rural area in the state of Pará and to describe the possible risk factors for infection. A total of 907 individuals responded to an epidemiological survey and gave blood samples collected for anti-HTLV-1/2 antibodies by immunoenzymatic assay (EIA). The serum-reactive samples were subjected to confirmation by an in-line assay (Inno-Lia) and by proviral DNA screening using real-time PCR (qPCR). The total prevalence was 0.8% (7/907) for HTLV-1/2 (CI: 0.2-1.3%), with 0.66% HTLV-1 and 0.11% HTLV-2. The prevalence by sex was 0.7% in women (4/565) and 0.9% in men (3/342). Among seropositive patients, 83.3% (5/7) reported being sexually active, and 57.1% (4/7) reported not having the habit of using condoms during their sexual relations. Intrafamily infection was also observed. The results reinforce the need for public policies to prevent and block the spread of HTLV, especially in riparian communities that are subject to difficulties in accessing the Unified Health System (Sistema Único de Saúde/SUS) because infected individuals need clinical monitoring for surveillance and early diagnosis of symptoms associated with HTLV-1.
Assuntos
Infecções por HTLV-I , Infecções por HTLV-II , Vírus Linfotrópico T Tipo 1 Humano , Feminino , Humanos , Masculino , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-II/diagnóstico , Infecções por HTLV-II/epidemiologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 2 Humano/genética , Prevalência , Fatores de Risco , População RuralRESUMO
A multi-epitope protein expressed in a prokaryotic system, including epitopes of Env, Gag, and Tax proteins of both HTLV-1 and HTLV-2 was characterized for HTLV-1/2 serological screening. This tool can contribute to support the implementation of public policies to reduce HTLV-1/2 transmission in Brazil, the country with the highest absolute numbers of HTLV-1/2 infected individuals. The chimeric protein was tested in EIA using serum/plasma of HTLV-infected individuals and non-infected ones from four Brazilian states, including the North and Northeast regions (that present high prevalence of HTLV-1/2) and Southeast region (that presents intermediate prevalence rates) depicting different epidemiological context of HTLV-1/2 infection in our country. We enrolled samples from Pará (n = 114), Maranhão (n = 153), Minas Gerais (n = 225) and São Paulo (n = 59) states; they are from blood donors' candidates (Pará and Minas Gerais), pregnant women (Maranhão) and HIV+/high risk for sexually transmitted infection (STI; São Paulo). Among the HTLV-1/2 positive sera, there were co-infections with viral (HTLV-1 + HTLV-2, HIV, HCV, and HBV), bacterial (Treponema pallidum) and parasitic (Trypanosoma cruzi, Schistosma mansoni, Strongyloides stercoralis, Entamoeba coli, E. histolytica, and Endolimax nana) pathogens related to HTLV-1/2 co-morbidities that can contribute to inconclusive diagnostic results. Sera positive for HIV were included among the HTLV-1/2 negative samples. Considering both HTLV-1 and HTLV-2-infected samples from all states and different groups (blood donor candidates, pregnant women, and individuals with high risk for STI), mono or co-infected and HTLV-/HIV+, the test specificity ranged from 90.09 to 95.19% and the sensitivity from 82.41 to 92.36% with high accuracy (ROC AUC = 0.9552). This multi-epitope protein showed great potential to be used in serological screening of HTLV-1 and HTLV-2 in different platforms, even taking into account the great regional variation and different profile of HTLV-1 and HTLV-2 mono or co-infected individuals.