Prevalence and characteristics of HTLV-associated uveitis in patients from Bahia, an endemic area for HTLV - 1 in Brazil.

BACKGROUND: HTLV-1-associated uveitis (HAU) is an inflammatory reaction of the choroid, retina, optic nerve and vitreous that can lead to vision impairment. The worldwide prevalence of HAU varies widely. OBJECTIVE: To determine the prevalence of HAU in patients from Salvador, Bahia-Brazil, and describe uveitis type and associated symptoms. METHODS: Cross-sectional analytical study to determine the prevalence of uveitis in HTLV-1-infected patients recruited in Bahia, Brazil, a region considered endemic for HTLV-1. Patients were enrolled at a local reference center for HTLV (infected) and at an outpatient ophthalmology clinic (noninfected group). All patients were examined by the same ophthalmologist following a single protocol. Prevalence ratios (PR) were calculated. RESULTS: A total of 168 consecutively examined HTLV-1-infected patients and 410 noninfected patients (randomly selected) were included. Females predominated (82.1%) in the HTLV-1-infected group (versus 64.4% in the uninfected group) (p < 0.001). The mean age of infected and uninfected patients was 53.2 and 62.8 years, respectively (p < 0.001). The prevalence of uveitis in HTLV-1+ and HTLV-1- patients was 7.14% and 0.73%, respectively (PR = 9.76; 95CI%:2.79-34.15; p < 0.01). Bilateral intermediate uveitis, associated with symptoms including visual disturbances and floaters, was most commonly identified in the HTLV-1-infected patients, whereas unilateral anterior uveitis, in association with symptoms such as blurring and ocular pain, was more common in the uninfected group. CONCLUSION: The prevalence of uveitis in patients with HTLV-1 was markedly higher than in uninfected subjects. HAU patients were mostly asymptomatic and exhibited bilateral presentation, with uveitis more frequently localized in the intermediate chamber.

Human T Cell Lymphotropic Virus Type 1 Global Prevalence Associated with the Human Development Index: Systematic Review with Meta-Analysis.

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.

Economic analysis of antenatal screening for human T-cell lymphotropic virus type 1 in Brazil: an open access cost-utility model

Background Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes severe diseases, such as aggressive cancer or progressive neurological disease. HTLV-1 affects mainly people in areas with low human development index and can be transmitted from mother to child, primarily through breastfeeding. Refraining from breastfeeding is an effective intervention to reduce the risk of infection in infants. However, HTLV-1 antenatal screening is not offered globally. According to WHO, the scarcity of cost-effectiveness studies is considered one of the major barriers to the implementation of policies to prevent HTLV-1 infection. Therefore, this study aimed to assess the cost-effectiveness of antenatal screening and postnatal interventions to prevent HTLV-1 mother-to-child transmission in Brazil and to develop an open-access, editable, mathematical model that can be used by other countries and regions to assess different scenarios. Methods In this cost-utility analysis, we constructed a decision tree and a Markov model to assess the cost-effectiveness of HTLV-1 antenatal screening and postnatal interventions (ie, avoidance of breastfeeding, by suppression of lactation with cabergoline, and provision of formula feed) to reduce transmission. For our model, we used data from Brazil and we took the perspective of the public health-care system to estimate costs. Findings The implementation of both screening and interventions would result in the prevention of 1039 infections in infants every year in Brazil with an incremental cost-effectiveness ratio (ICER) of US$11415 per quality-adjusted lifeyear (QALY). 88% of all probabilistic sensitivity analysis simulations had ICER values lower than the Brazilian costeffectiveness threshold ($18 107·74 per QALY). HTLV-1 prevalence in pregnant women, the risk of HTLV-1 transmission when breastfeeding lasts for 6 months or more, and the cost of screening tests were the variables with the largest effect on ICER. Interpretation HTLV-1 antenatal screening is cost-effective in Brazil. An open-access model was developed, and this tool could be used to assess the cost-effectiveness of such policy globally, favouring the implementation of interventions to prevent HTLV-1 mother-to-child transmission worldwide. (AU)

Integrative and Multidisciplinary Care for People Living With Human T-Cell Lymphotropic Virus in Bahia, Brazil: 20 Years of Experience.

Brazil is home to the highest absolute number of human T-cell lymphotropic virus type-1 (HTLV-1)-infected individuals worldwide; the city of Salvador, Bahia, has the highest prevalence of HTLV-1 infection in Brazil. Due to the complex nature of several diseases associated with this retrovirus, a multidisciplinary health care approach is necessary to care for people living with HTLV-1. The Bahia School of Medicine and Public Health's Integrative Multidisciplinary HTLV Center (CHTLV) has been providing support to people living with HTLV and their families since 2002, striving to ensure physical and mental well-being by addressing biopsychosocial aspects, providing clinical care and follow-up, including to pregnant/postpartum women, as well as comprehensive laboratory diagnostics, psychological therapy, and counseling to family members. To date, CHTLV has served a total of 2,169 HTLV-infected patients. The average patient age is 49.8 (SD 15.9) years, 70.3% are female, most are considered low-income and have low levels of education. The majority (98.9%) are HTLV-1 cases, and approximately 10% have been diagnosed with tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM), while 2.2% have infective dermatitis and 1.1% have adult T-cell lymphoma. In all, 178 pregnant/postpartum women [mean age: 32.7 (±6.5) years] have received care at CHTLV. Regarding vertical transmission, 53% of breastfed infants screened for HTLV tested positive in their second year of life, nearly 18 times the rate found in non-breastfed infants. This article documents 20 years of experience in implementing an integrative and multidisciplinary care center for people living with HTLV in Bahia, Brazil. Still, significant challenges remain regarding infection control, and HTLV-infected individuals continue to struggle with the obtainment of equitable and efficient healthcare.

Efficacy of Corticosteroid Therapy for HTLV-1-Associated Myelopathy: A Randomized Controlled Trial (HAMLET-P).

Corticosteroids are most commonly used to treat HTLV-1-associated myelopathy (HAM); however, their clinical efficacy has not been tested in randomized clinical trials. This randomized controlled trial included 8 and 30 HAM patients with rapidly and slowly progressing walking disabilities, respectively. Rapid progressors were assigned (1:1) to receive or not receive a 3-day course of intravenous methylprednisolone in addition to oral prednisolone therapy. Meanwhile, slow progressors were assigned (1:1) to receive oral prednisolone or placebo. The primary outcomes were a composite of ≥1-grade improvement in the Osame Motor Disability Score or ≥30% improvement in the 10 m walking time (10 mWT) at week 2 for rapid progressors and changes from baseline in 10 mWT at week 24 for slow progressors. In the rapid progressor trial, all four patients with but only one of four without intravenous methylprednisolone achieved the primary outcome (p = 0.14). In the slow progressor trial, the median changes in 10 mWT were -13.8% (95% CI: -20.1--7.1; p < 0.001) and -6.0% (95% CI: -12.8-1.3; p = 0.10) with prednisolone and placebo, respectively (p for between-group difference = 0.12). Whereas statistical significance was not reached for the primary endpoints, the overall data indicated the benefit of corticosteroid therapy. (Registration number: UMIN000023798, UMIN000024085).

HIV/Aids and COVID-19 in Brazil: in four decades, two antithetical approaches to face serious pandemics

In the space of four decades, Brazil has faced two serious pandemics: human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and Coronavirus disease 2019 (COVID-19). The country's response to HIV/AIDS was coordinated by several stakeholders and recognised the importance of scientific evidence in guiding decision-making, and a network offering monitoring and antiretroviral treatment was provided through coordinated efforts by the country's universal health system. Conversely, the lack of a centrally coordinated strategy and misalignment between government ministries regarding the COVID-19 pandemic response, together with the denial of scientific evidence, promotion of ineffective treatments and insufficient vaccination efforts, have all led to the uncontrolled spread of infection, the near-total collapse of the health system and excess deaths.

Clinical and laboratory findings of acute Zika virus infection in patients from Salvador during the first Brazilian epidemic

Abstract Several major epidemics of Zika fever, caused by the ZIKA virus (ZIKV), have emerged in Brazil since early 2015, eventually spreading to other countries on the South American continent. The present study describes the clinical manifestations and laboratory findings of patients with confirmed acute ZIKV infection during the first epidemic that occurred in Salvador, Brazil. All included patients were seen at the emergency room of a private tertiary hospital located in Salvador, Brazil from 2015 through 2017. Patients were considered eligible if signs of systemic viral febrile disease were present. All individuals were tested for ZIKV and Chikungunya infection using PCR, while rapid test was used to detect Dengue virus antibodies or, alternatively, the NS1 antigen. A diagnosis of acute ZIKV infection was confirmed in 78/434 (18%) individuals with systemic viral febrile illness. Positivity was mainly observed in blood, followed by saliva and urine. Coinfection with Chikungunya and/or Dengue virus was detected in 5% of the ZIKV-infected patients. The most frequent clinical findings were myalgia, arthralgia and low-grade fever. Laboratory analysis demonstrated normal levels of hematocrit, platelets and liver enzymes. In summary, in acute settings where molecular testing remains unavailable, clinicians face difficulties to confirm the diagnosis of ZIKV infection, as they rely only on clinical examinations and conventional laboratory tests.

Distribution of Human T-Lymphotropic Virus (HTLV) and Hepatitis C Co-infection in Bahia, Brazil.

Both Human T-lymphotropic virus type 1 (HTLV-1) and hepatitis C virus (HCV) are endemic in Brazil. In Salvador, the capital of the state of Bahia, 2% and 1.5% of the general population is infected with HTLV-1 or HCV. This study aimed to estimate the prevalence and the distribution of HTLV/HCV coinfection in Bahia. This cross-sectional study was conducted at the Central Laboratory of Public Health for the state of Bahia (LACEN-BA). All samples in the LACEN database submitted to serological testing for anti-HCV (chemiluminescence) and anti-HTLV-1/2 (chemiluminescence/ELISA and Western blot) from 2004 to 2013 were included. Infection rate was expressed as the number of infected individuals per 100,000 inhabitants in a given municipality; municipalities were grouped by microregion for further analysis. A total of 120,192 samples originating from 358 of the 417 municipalities in Bahia (85.8%) were evaluated. The overall HCV coinfection rate in HTLV-positive was 14.31% [2.8 (ranging from 0.4 to 8.0) per 100,000 inhabitants.] Twenty-one (5%) of the municipalities reported at least one case of HTLV/HCV coinfection. Most cases (87%) were concentrated in three microregions (Salvador: 79%, Ilhéus/Itabuna: 5%, Porto Seguro: 3%). Coinfection occurred more frequently in males (51%) with a mean age of 59 [(IQR): 46-59] years. HTLV/HCV coinfection in the state of Bahia was more frequently found among males living in the microregions of Salvador, Ilhéus/Itabuna and Porto Seguro, all of which are known to be endemic for HTLV infection.

Evidence of New Endemic Clusters of Human T-Cell Leukemia Virus (HTLV) Infection in Bahia, Brazil.

BACKGROUND: Salvador, Bahia (northeastern Brazil), has been identified as the epicenter of Human T-cell leukemia virus Human T-cell leukemia virus (HTLV) type 1 infection in the country. This study aims to estimate the rate of HTLV infection and the geographical distribution of this virus in this state. METHODS: All HTLV tests (chemiluminescence/ELISA assays/Western Blotting) performed in the Central Laboratory of Public Health of Bahia (LACEN) from 2004 to 2013 were included. Data was extracted from LACEN's database using high volume extract, transformation and load throughput. Infection rate was expressed as the number of infected individuals per 100,000 inhabitants considering municipalities grouped in microregions and/or mesoregions as the unit of analysis. RESULTS: A total of 233,876 individuals were evaluated. Individuals were from 394 out of 417 municipalities of Bahia (94.5%). HTLV chemiluminescence/ELISA assay was found to be reactive for 3,138 individuals from whom 2,323 had WB results (1,978 positives, 62 negative and 282 indeterminate). Out of 1978 reactive samples, 1,813 (91.7%) were positive for HTLV-1, 58 (2.9%) for HTLV-2 and 107 (5.4%) were for both HTLV-1 and HTLV-2. The cumulative mean rate of HTLV-positive cases in Bahia was 14.4 per 100,000 inhabitants. Three microregions presented rates >20 HTLV-positive cases/100,000 inhabitants: Barreiras (24.83 cases per 100,000 inhabitants), Salvador (22.90 cases per 100,000 inhabitants), and Ilhéus-Itabuna (22.60 cases per 100,000 inhabitants). CONCLUSION: HTLV infection is disseminated in the state of Bahia, with an overall moderate rate of infection. Further studies should be conducted to characterize the epidemiological and clinical profile of HTLV-infected individuals better and to propose effective prevention measures.

Functional capacity of natural killer cells in HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients.

BACKGROUND: Natural killer (NK) cells are part of the innate immune system and provide surveillance against viruses and cancers. The ability of NK cells to kill virus-infected cells depends on the balance between the effects of inhibitory and activating NK cell receptors. This study aimed to investigate the phenotypic profile and the functional capacity of NK cells in the context of HTLV-1 infection. METHODS: This cross-sectional study sequentially recruited HTLV-1 infected individuals with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and asymptomatic HTLV-1 (AS) from the Integrated and Multidisciplinary HTLV Center in Salvador, Brazil. Blood samples from healthy blood donors served as controls. NK cell surface receptors (NKG2D, KIR2DL2/KIR2DL3, NKp30, NKG2A, NKp46, TIM-3 and PD-1), intracellular cytolytic (Granzyme B, perforin) and functional markers (CD107a for degranulation, IFN-γ) were assayed by flow cytometry in the presence or absence of standard K562 target cells. In addition, cytotoxicity assays were performed in the presence or absence of anti-NKp30. RESULTS: The frequency of NKp30+ NK cells was significantly decreased in HAM/TSP patients [58%, Interquartile Range (IQR) 30-61] compared to controls (73%, IQR 54-79, p = 0.04). The production of cytolytic (perforin, granzyme B) and functional markers (CD107a and IFN-γ) was higher in unstimulated NK cells from HAM/TSP and AS patients compared to controls. By contrast, stimulation with K562 target cells did not alter the frequency of CD107a+ NK cells in HAM/TSP subjects compared to the other groups. Blockage of the NKp30 receptor was shown to decrease cytotoxic activity (CD107a) and IFN-γ expression only in asymptomatic HTLV-1-infected individuals. CONCLUSIONS: NK cells from individuals with a diagnosis of HAM/TSP present decreased expression of the activating receptor NKp30, in addition to elevated degranulation activity that remained unaffected after blocking the NKp30 receptor.

Revisiting Keratoconjunctivitis sicca associated with Human T-Cell Lymphotropic Virus Type 1: prevalence, clinical aspects and proviral load.

BACKGROUND: The prevalence of keratoconjunctivitis sicca (KCS) associated with Human T-Cell Lymphotropic Virus Type 1 (HTLV-1) (HTLV-1/KCS) has been estimated at around 37%, but its clinical manifestations are poorly described. PURPOSE: To determine the prevalence and associated factors of HTLV-1/KCS in a large cohort of HTLV-1-infected individuals living in Salvador, Brazil. METHODS: A cross-sectional study was conducted between June 2004 and September 2017 at the Integrative and Multidisciplinary Center for HTLV in Salvador, Bahia-Brazil. Data from 758 HTLV-1-infected patients was collected. A complete ophthalmologic examination was performed in both eyes. Lacrimal function was evaluated by breakup time, Rose Bengal and Schirmer I Tests. KCS diagnosis was considered in the presence of at least two out of three positive tests. HTLV-1 proviral load Crude and Adjusted Prevalence Rates (PR) with 95% Confidence Intervals (95% CI) were estimated using multivariate Poisson Regression with robust error variance. RESULTS: The overall prevalence of KCS was 31.7%, with higher rates observed in HTLV-1-associated myelopathy/tropical spastic paraparesis patients (crude PR: 1.84; CI95%: 1.50-2.26) even after adjusting for age, sex, time of HTLV-1 diagnosis and schooling (adjusted PR: 1.63; CI95%: 1.31-2.02). Proviral load, low corrected visual acuity, burning and/or pain and itching were all significantly higher in patients with KCS. CONCLUSION: Burning and/or pain and itching and low corrected visual acuity were the most common alterations of HTLV-1/KCS. High Proviral load was found to be associated with the presence of KCS. It is strongly recommended that HTLV-1 patients undergo periodic ophthalmologic examination to promote the early diagnosis of KCS and prevent the consequences associated with dry eye disease.

The Role of NK Cells in the Control of Viral Infection in HTLV-1 Carriers.

The cytotoxic activities of CD8+ T cells have been considered the main defense mechanism against the human T lymphotropic virus type 1 (HTLV-1). As with CD8+ T cells, NK cells can perform cytotoxic degranulation with production of cytotoxic mediators, such as perforins and granzymes. NK cells are also responsible for antibody-dependent cellular cytotoxicity (ADCC) against infected cells, but few studies have evaluated the role of NK cells in HTLV-1 infection. The aim of this study was to characterize the subsets and measure the frequency of NK cells in HTLV-1 carriers (HC) and in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and correlate these findings with the proviral load and development of HAM/TSP. The diagnosis of HTLV-1 infection was performed with a detection antibody against viral antigens by ELISA and confirmed by Western blot. Phenotypic characterization of NK cells was performed by flow cytometry. The frequencies of CD56+, CD56+CD3-, CD56+CD16+, and CD56dim cells were decreased in HAM/TSP patients. The frequency of CD56+CD3- cells was inversely correlated with proviral load in HC but not in HAM/TSP patients. HAM/TSP patients showed decreased frequency of CD56+ and CD56dim cells expressing CD16, the main receptor for ADCC. These data indicate that NK cells may play a key role in the control of HTLV-1 infection by preventing the progression of HC to HAM/TSP.

Evaluation of the cervicovaginal environment in asymptomatic Human T-cell lymphotropic virus type 1 infected women.

INTRODUCTION: Human T-cell lymphotropic virus type 1 (HTLV-1) is sexually transmitted and causes persistent infection. This virus induces activation of the immune system and production of inflammatory cytokines. This study aimed to assess the cytokine profile and cytopathological findings in the cervicovaginal fluid of asymptomatic HTLV-1-infected women. METHODS: HTLV-1-infected and uninfected women were selected at the Centro de Atendimento ao Portador de HTLV in Salvador-Brazil. None of the included HTLV-1-infected women reported any HTLV-1-associated diseases. All volunteers underwent gynecological examination to collect cervicovaginal fluid. Cytokine quantification was performed using the Cytometric Bead Array (CBA) Human Th1/Th2/Th17 kit. Light microscopy was used to evaluate cervicovaginal cytopathology. In addition, proviral load in cervicovaginal fluid and peripheral blood was measured by real-time quantitative polymerase chain reaction. RESULTS: 112 women (63 HTLV-1-infected and 49 uninfected) were evaluated. No differences were found with respect to cytopathological cervicovaginal findings between the groups. IL-2, TNF, IL-4, IL-10, and IL-17 levels were significantly higher in cervicovaginal fluid of the HTLV-1-infected women than in uninfected women (p<0.05). Conversely, IFN-γ was found to be lower in the HTLV-1-infected women (p<0.001) compared to uninfected individuals. Cervicovaginal proviral load was detectable in 53% of the HTLV-1-infected women and was found to be consistently lower than the proviral load in peripheral blood. CONCLUSIONS: HTLV-1 infection induces immune activation in cervicovaginal environment, characterized by elevated concentrations of Th1, Th2, and IL17 in the cervicovaginal fluid.

Revisiting Keratoconjunctivitis sicca associated with Human T-Cell Lymphotropic Virus Type 1: prevalence, clinical aspects and proviral load

ABSTRACT Background: The prevalence of keratoconjunctivitis sicca (KCS) associated with Human T-Cell Lymphotropic Virus Type 1 (HTLV-1) (HTLV-1/KCS) has been estimated at around 37%, but its clinical manifestations are poorly described. Purpose: To determine the prevalence and associated factors of HTLV-1/KCS in a large cohort of HTLV-1-infected individuals living in Salvador, Brazil. Methods: A cross-sectional study was conducted between June 2004 and September 2017 at the Integrative and Multidisciplinary Center for HTLV in Salvador, Bahia-Brazil. Data from 758 HTLV-1-infected patients was collected. A complete ophthalmologic examination was performed in both eyes. Lacrimal function was evaluated by breakup time, Rose Bengal and Schirmer I Tests. KCS diagnosis was considered in the presence of at least two out of three positive tests. HTLV-1 proviral load Crude and Adjusted Prevalence Rates (PR) with 95% Confidence Intervals (95% CI) were estimated using multivariate Poisson Regression with robust error variance. Results: The overall prevalence of KCS was 31.7%, with higher rates observed in HTLV-1-associated myelopathy/tropical spastic paraparesis patients (crude PR: 1.84; CI95%: 1.50-2.26) even after adjusting for age, sex, time of HTLV-1 diagnosis and schooling (adjusted PR: 1.63; CI95%: 1.31-2.02). Proviral load, low corrected visual acuity, burning and/or pain and itching were all significantly higher in patients with KCS. Conclusion: Burning and/or pain and itching and low corrected visual acuity were the most common alterations of HTLV-1/KCS. High Proviral load was found to be associated with the presence of KCS. It is strongly recommended that HTLV-1 patients undergo periodic ophthalmologic examination to promote the early diagnosis of KCS and prevent the consequences associated with dry eye disease.

Evaluation of the cervicovaginal environment in asymptomatic Human T-cell lymphotropic virus type 1 infected women

ABSTRACT Introduction: Human T-cell lymphotropic virus type 1 (HTLV-1) is sexually transmitted and causes persistent infection. This virus induces activation of the immune system and production of inflammatory cytokines. This study aimed to assess the cytokine profile and cytopathological findings in the cervicovaginal fluid of asymptomatic HTLV-1-infected women. Methods: HTLV-1-infected and uninfected women were selected at the Centro de Atendimento ao Portador de HTLV in Salvador-Brazil. None of the included HTLV-1-infected women reported any HTLV-1-associated diseases. All volunteers underwent gynecological examination to collect cervicovaginal fluid. Cytokine quantification was performed using the Cytometric Bead Array (CBA) Human Th1/Th2/Th17 kit. Light microscopy was used to evaluate cervicovaginal cytopathology. In addition, proviral load in cervicovaginal fluid and peripheral blood was measured by real-time quantitative polymerase chain reaction. Results: 112 women (63 HTLV-1-infected and 49 uninfected) were evaluated. No differences were found with respect to cytopathological cervicovaginal findings between the groups. IL-2, TNF, IL-4, IL-10, and IL-17 levels were significantly higher in cervicovaginal fluid of the HTLV-1-infected women than in uninfected women (p < 0.05). Conversely, IFN-γ was found to be lower in the HTLV-1-infected women (p < 0.001) compared to uninfected individuals. Cervicovaginal proviral load was detectable in 53% of the HTLV-1-infected women and was found to be consistently lower than the proviral load in peripheral blood. Conclusions: HTLV-1 infection induces immune activation in cervicovaginal environment, characterized by elevated concentrations of Th1, Th2, and IL17 in the cervicovaginal fluid.

Case Report: Strongyloides stercoralis Hyperinfection in a Patient with HTLV-1: An Infection with Filariform and Rhabditiform Larvae, Eggs, and Free-Living Adult Females Output.

Strongyloides stercoralis is the main etiological agent of human strongyloidiasis. Severe strongyloidiasis is commonly associated to alcoholism, corticostereoid use, and human T cell lymphotropic virus type 1 (HTLV-1) coinfection. Herein, we report a case of a 13-year-old boy coinfected with S. stercoralis and HTLV-1, excreting several parasitic forms in the stool. The parasitological examination of his feces showed a large amount of filariform (about 3,000 larvae per gram of feces) and rhabditiform larvae (about 2,000 larvae per gram of feces). In addition, free-living adult females (about 50 parasites per gram of feces) and eggs (about 60 eggs per gram of feces) were detected. The main laboratory findings pointed to high immunoglobulin E (IgE) levels (228 UI/mL) and eosinophila (11.6%). The patient was treated with three courses of ivermectin (200 µg/kg twice, 2 weeks apart), achieving the parasitological cure. An increase of about 19 times in interleucin (IL)-17 level was observed following the parasitological cure, in addition to a decrease in the white blood cell, eosinophil counts, and IgE levels. This is the first case report, to our knowledge, in which an S. stercoralis adult free-living female was described in human feces and where an increase in IL-17 levels after Strongyloides treatment in a HTLV-1 coinfected individual was observed. This finding raises the need for further studies about IL-17 immunomodulation in S. stercoralis and HTLV-1 coinfected patients.

Performance of Commercially Available Serological Screening Tests for Human T-Cell Lymphotropic Virus Infection in Brazil.

Serological screening for human T-cell lymphotropic virus type 1 (HTLV-1) is usually performed using enzyme-linked immunosorbent assay (ELISA), particle agglutination, or chemiluminescence assay kits. Due to an antigen matrix improvement entailing the use of new HTLV antigens and changes in the format of HTLV screening tests, as well as newly introduced chemiluminescence assays (CLIAs), a systematic evaluation of the accuracy of currently available commercial tests is warranted. We aimed to assess the performance of commercially available screening tests for HTLV infection diagnosis. A diagnostic accuracy study was conducted on a panel of 397 plasma samples: 200 HTLV-negative plasma samples, 170 HTLV-positive plasma samples, and 27 plasma samples indeterminate by Western blotting (WB). WB-indeterminate samples (i.e., those yielding no specific bands for HTLV-1 and/or HTLV-2) were assessed by PCR, and the results were used to compare agreement among the commercially available ELISA screening tests. For performance analysis, WB-indeterminate samples were excluded, resulting in a final study panel of 370 samples. Three ELISA kits (Murex HTLV-1/2 [Murex], anti-HTLV-1/2 SYM Solution [SYM Solution], and Gold ELISA HTLV-1/2 [Gold ELISA]) and one CLIA kit (Architect rHTLV-1/2) were evaluated. All screening tests demonstrated 100% sensitivity. Concerning the HTLV-negative samples, the SYM Solution and Gold ELISA kits had specificity values of >99.5%, while the Architect rHTLV-1/2 test presented 98.1% specificity, followed by Murex, which had a specificity of 92.0%. Regarding the 27 samples with WB-indeterminate results, after PCR confirmation, all ELISA kits showed 100% sensitivity but low specificity. Accuracy findings were corroborated by the use of Cohen's kappa value, which evidenced slight and fair agreement between PCR analysis and ELISAs for HTLV infection diagnosis. Based on the data, we believe that all evaluated tests can be safely used for HTLV infection screening.

Performance of commercially available serological screening Tests for human T-Cell lymphotropic virus infection in Brazil

ABSTRACT Serological screening for human T-cell lymphotropic virus type 1 (HTLV-1) is usually performed using enzyme-linked immunosorbent assay (ELISA), particle agglutination, or chemiluminescence assay kits. Due to an antigen matrix improvement entailing the use of new HTLV antigens and changes in the format of HTLV screening tests, as well as newly introduced chemiluminescence assays (CLIAs), a systematic evaluation of the accuracy of currently available commercial tests is warranted. We aimed to assess the performance of commercially available screening tests for HTLV infection diagnosis. A diagnostic accuracy study was conducted on a panel of 397 plasma samples: 200 HTLV-negative plasma samples, 170 HTLV-positive plasma samples, and 27 plasma samples indeterminate by Western blotting (WB). WB-indeterminate samples (i.e., those yielding no specific bands for HTLV-1 and/or HTLV-2) were assessed by PCR, and the results were used to compare agreement among the commercially available ELISA screening tests. For performance analysis, WB-indeterminate samples were excluded, resulting in a final study panel of 370 samples. Three ELISA kits (Murex HTLV-1/2 [Murex], anti-HTLV-1/2 SYM Solution [SYM Solution], and Gold ELISA HTLV-1/2 [Gold ELISA]) and one CLIA kit (Architect rHTLV- 1/2) were evaluated. All screening tests demonstrated 100% sensitivity. Concerning the HTLV-negative samples, the SYM Solution and Gold ELISA kits had specificity values of 99.5%, while the Architect rHTLV-1/2 test presented 98.1% specificity, followed by Murex, which had a specificity of 92.0%. Regarding the 27 samples with WB-indeterminate results, after PCR confirmation, all ELISA kits showed 100% sensitivity but low specificity. Accuracy findings were corroborated by the use of Cohen's kappa value, which evidenced slight and fair agreement between PCR analysis and ELISAs for HTLV infection diagnosis. Based on the data, we believe that all evaluated tests can be safely used for HTLV infection screening.

Algorithm for dry eye disease diagnosis in individuals infected with human T-cell lymphotropic virus type 1.

PURPOSE: To evaluate the accuracy of lacrimal film tests and propose an algorithm for the diagnosis of dry eye disease in individuals infected with human T-cell lymphotropic virus type 1. METHODS: Ninety-six patients infected with human T-cell lymphotropic virus type 1 were enrolled in the study. To assess clinical complaints, patients completed the Ocular Surface Disease Index questionnaire. To evaluate lacrimal film quality, patients underwent the tear breakup time test, Schirmer I test, and Rose Bengal staining. Dry eye disease was diagnosed when at least two of the three test results were abnormal. The sensitivity, specificity, positive and negative predictive values, and overall accuracy of the questionnaire as well as of each test alone and combined in parallel and in series were determined. RESULTS: The most sensitive test was the tear breakup time test (98%), whereas the most specific was the Schirmer I test (100%). Rose Bengal staining had the highest overall accuracy (88.64%), whereas the Ocular Surface Disease Index had the lowest overall accuracy (62.65%). The tear breakup time test, Schirmer I test, and Ocular Surface Disease Index combined in parallel showed increased sensitivity and decreased specificity for all tests. In contrast, when combined in series, these tests demonstrated increased specificity and decreased sensitivity. CONCLUSION: This study shows the need to use multiple tests to evaluate tear film quality and include a symptom questionnaire as part of the diagnostic algorithm for dry eye disease.

Algorithm for dry eye disease diagnosis in individuals infected with human T-cell lymphotropic virus type 1 / Algoritmo para o diagnóstico da doença do olho seco em indivíduos infectados com vírus linfotrópico de células-T humanas tipo 1

ABSTRACT Purpose: To evaluate the accuracy of lacrimal film tests and propose an algorithm for the diagnosis of dry eye disease in individuals infected with human T-cell lymphotropic virus type 1. Methods: Ninety-six patients infected with human T-cell lymphotropic virus type 1 were enrolled in the study. To assess clinical complaints, patients completed the Ocular Surface Disease Index questionnaire. To evaluate lacrimal film quality, patients underwent the tear breakup time test, Schirmer I test, and Rose Bengal staining. Dry eye disease was diagnosed when at least two of the three test results were abnormal. The sensitivity, specificity, positive and negative predictive values, and overall accuracy of the questionnaire as well as of each test alone and combined in parallel and in series were determined. Results: The most sensitive test was the tear breakup time test (98%), whereas the most specific was the Schirmer I test (100%). Rose Bengal staining had the highest overall accuracy (88.64%), whereas the Ocular Surface Disease Index had the lowest overall accuracy (62.65%). The tear breakup time test, Schirmer I test, and Ocular Surface Disease Index combined in parallel showed increased sensitivity and decreased specificity for all tests. In contrast, when combined in series, these tests demonstrated increased specificity and decreased sensitivity. Conclusion: This study shows the need to use multiple tests to evaluate tear film quality and include a symptom questionnaire as part of the diagnostic algorithm for dry eye disease.

RESUMO Objetivo: Avaliar a precisão da propedêutica do filme lacrimal e propor um algoritmo para o diagnóstico da doença do olho seco em indivíduos infectados com Vírus linfotrópico de células-T humanas tipo 1. Métodos: Noventa e seis pacientes infectados com o vírus linfotrópico de células T humana tipo 1 foram incluídos no estudo. Para avaliar sintomatologia, os pacientes responderam o questionário Índice para Doenças da Superfície Ocular. A fim de avaliar a qualidade do filme lacrimal, os pacientes foram submetidos ao teste de ruptura do filme lacrimal, teste de Schirmer I e coloração com Rosa Bengala. A doença do olho seco foi diagnosticada quando, pelo menos, dois dos testes ruptura do filme lacrimal, teste de Schirmer I e coloração com Rosa Bengala) eram anormais. Foram determinados sensibilidade, especificidade, valor preditivo positivo e negativo e acurácia do questionário e de cada teste sozinho e combinados em paralelo e em série. Resultados: O teste de ruptura do filme lacrimal foi o mais sensível (98%) e o teste de Schirmer I foi o mais específico (100%). A maior acurácia foi encontrada no teste de coloração com Rosa Bengala (88,64%), enquanto sintomas avaliados usando o questionário Índice para Doenças da Superfície Ocular teve a menor acurácia geral (62,65%). O teste de ruptura do filme lacrimal, teste de Schirmer I e Questionário de Doença da Superfície Ocular quando combinados em paralelo mostraram um aumento da sensibilidade e uma diminuição na especificidade de todos os testes. Por outro lado, combinados em série, teste de ruptura do filme lacrimal, Schirmer I e questionário Índice para Doenças da Superfície Ocular tiveram um aumento na especificidade e sensibilidade diminuída. Conclusão: Este estudo apontou a necessidade de utilizar mais do que um teste para avaliar a qualidade do filme lacrimal, bem como utilizar um questionário de sintomas como parte do algoritmo de diagnóstico para doença do olho seco.