Comprehensive analysis of early T cell responses to acute Zika Virus infection during the first epidemic in Bahia, Brazil.

BACKGROUND: In most cases, Zika virus (ZIKV) causes a self-limited acute illness in adults, characterized by mild clinical symptoms that resolve within a few days. Immune responses, both innate and adaptive, play a central role in controlling and eliminating virus-infected cells during the early stages of infection. AIM: To test the hypothesis that circulating T cells exhibit phenotypic and functional activation characteristics during the viremic phase of ZIKV infection. METHODS: A comprehensive analysis using mass cytometry was performed on peripheral blood mononuclear cells obtained from patients with acute ZIKV infection (as confirmed by RT-PCR) and compared with that from healthy donors (HD). The frequency of IFN-γ-producing T cells in response to peptide pools covering immunogenic regions of structural and nonstructural ZIKV proteins was quantified using an ELISpot assay. RESULTS: Circulating CD4+ and CD8+ T lymphocytes from ZIKV-infected patients expressed higher levels of IFN-γ and pSTAT-5, as well as cell surface markers associated with proliferation (Ki-67), activation ((HLA-DR, CD38) or exhaustion (PD1 and CTLA-4), compared to those from HD. Activation of CD4+ and CD8+ memory T cell subsets, including Transitional Memory T Cells (TTM), Effector Memory T cells (TEM), and Effector Memory T cells Re-expressing CD45RA (TEMRA), was prominent among CD4+ T cell subset of ZIKV-infected patients and was associated with increased levels of IFN-γ, pSTAT-5, Ki-67, CTLA-4, and PD1, as compared to HD. Additionally, approximately 30% of ZIKV-infected patients exhibited a T cell response primarily directed against the ZIKV NS5 protein. CONCLUSION: Circulating T lymphocytes spontaneously produce IFN-γ and express elevated levels of pSTAT-5 during the early phase of ZIKV infection whereas recognition of ZIKV antigen results in the generation of virus-specific IFN-γ-producing T cells.

Comparative Study on Anti-VEGF in Wet Age-Related Macular Degeneration in the Setting Based on Lean Methodology from the Bari Intravitreal Injection Registry (BIVIR).

INTRODUCTION: Optimizing treatment protocols for wet age-related macular degeneration (wAMD) is an ongoing challenge, as it involves a delicate balance between achieving therapeutic efficacy and minimizing invasive procedures' frequency. This study aimed to apply the Lean methodology and evaluate the effectiveness of this new setting on intravitreal therapy for wAMD, employing different anti-vascular endothelial growth factors (VEGF) drugs (bevacizumab, brolucizumab, aflibercept, ranibizumab), drawing data from the Bari Intravitreal Injections Registry (BIVIR). METHODS: This was a retrospective, monocentric, nonrandomized, comparative study. Lean methodology was employed to design the new setting and the BIVIR collected information from electronic medical records. Clinical data of four groups, stratified based on the first-line anti-VEGF agents used, were compared. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) changes were compared between the four groups at 3 and 12 months. RESULTS: Out of 4990 eyes and 41,323 intravitreal injections (IVs) recorded in BIVIR, 1421 eyes of 1182 patients were included. The mean number of IVs in first year was 6.1 ± 2.5, with no significant differences among the four subgroups. The mean change in BCVA was + 6.2 letters [95% confidence interval (CI) 5.6-6.8] after two IVs, and + 5.9 (95% CI 5.1-6.8) letters after three IVs; at three months, brolucizumab was associated with a greater mean increase in BCVA than bevacizumab (p = 0.050); aflibercept (p = 0.044) and ranibizumab p = 0.047). At the 1-year follow-up, the mean change was + 6.3 letters (95% CI 5.4-7.2), brolucizumab and ranibizumab were associated with a superior improvement in BCVA compared to aflibercept (p = 0.033). Regarding the CRT, a significant reduction was observed in the subgroup treated with brolucizumab at the 3-month follow-up, compared to bevacizumab (p = 0.003), aflibercept (p = 0.015), and ranibizumab (p < 0.001); Aflibercept exhibited a superior effect than ranibizumab (p = 0.001). At 1-year follow-up, aflibercept resulted in a more significant reduction of macular thickness compared to ranibizumab (p = 0.016) while no significant differences were observed among the other drugs. CONCLUSIONS: Our practical experience showed the effectiveness of the new setting in the treatment of wAMD. This comparative study at 1 year suggested a predominant brolucizumab efficacy on functional outcomes. In addition, brolucizumab and aflibercept appeared to have similar efficacy in fluid control.

Optical coherence tomography biomarkers indicating visual enhancement in diabetic macular edema resolved through anti-VEGF therapy: OCT biomarkers in resolved DME.

PURPOSE: to investigate the structural features and extended visual results in eyes affected by diabetic retinopathy (DR) and diabetic macular edema (DME) that have been successfully treated with anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Individuals (39 eyes of 39 patients) who had undergone long-term follow-up and demonstrated evidence of resolved DME after at least 2 years of follow-up following the initiation of anti-VEGF therapy were included. During the ""study visit"", structural OCT scans were examined to assess qualitative features indicative of neuroretina or retinal pigment epithelium distress. Additionally, a quantitative assessment of the inner and outer retinal thicknesses was conducted for topographical analysis. RESULTS: The most robust qualitative association observed with BCVA at the "study visit" was linked to the presence of DRIL (p = 0.043) and the appearance of the ELM. (p = 0.045). Regarding quantitative parameters, a strong correlation was noted between the visual acuity during the "study visit" and the foveal and parafoveal thicknesses of both the inner and outer retina (p < 0.001). CONCLUSIONS: Changes in the status of ELM, the presence of DRIL, and the thicknesses of the foveal and parafoveal regions can act as OCT biomarkers, signifying prolonged visual improvements in eyes that have experienced resolved DME after undergoing anti-VEGF therapy.

Choroidal remodeling following different anti-VEGF therapies in neovascular AMD.

The purpose of this study was to investigate choroidal morphology remodeling in AMD-associated type 1 macular neovascularization using two different anti-VEGF drugs. We registered 73 treatment-naïve eyes with a diagnosis of exudative AMD and type 1 MNV. Patients received 3 monthly intravitreal aflibercept (n = 36, aflibercept group [AG]) or brolucizumab (n = 37, brolucizumab group [BG]). Baseline best-corrected visual acuity (BCVA) and anatomical (structural optical coherence tomography) parameters were collected at "T1 control", before the loading phase (LP) of intravitreal injection, and at "T2 control", 1 month after the last injection. The main outcomes measured were choroidal vascularity index (CVI), sub-foveal choroidal thickness (SFCT), and central macular thickness (CMT). Our results displayed significant SFCT reduction in both groups between T1 and T2 (p < 0.05), We did not find choroidal vascularity modifications (p > 0.05) after the loading aflibercept injections. Moreover, only the BG displayed a significant choroidal remodeling (stromal choroidal area [SCA], total choroidal area [TCA] and CVI) at T2 (p < 0.05). In particular, a relevant stromal and total choroidal volume reduction was noted, accompanied by an increase in CVI. To conclude, the latter modifications of the choroidal morphology were found significant between two groups (p < 0.05). Our analysis showed a significant impact of brolucizumab on choroidal morphology in eyes affected by type 1 nAMD. This effect was found relevant when compared with aflibercept.

Anterior chamber bleeding due to intravitreal dexamethasone implant sclerotomy without vitreous hemorrhage.

BACKGROUND: Anterior Chamber bleeding without vitreous hemorrhage had been described after the removal of 23G vitrectomy cannulas. We report the case of an anterior chamber bleeding after an intravitreal Dexamethasone implant. CASE REPORT: One patient with macular edema due to central retinal vein occlusion in a vitrectomized eye underwent an intravitreal Dexamethasone implant. After the injection the patient suffered from anterior chamber bleeding without signs of vitreous hemorrhage. The complication resolved with a conservative treatment. CONCLUSION: Anterior Chamber bleeding is a possible complication of dexamethasone implant, that can be treated in a conservative way.

The Impact of Diabetic Retinopathy on the Choriocapillaris in Neovascular AMD.

Purpose: To investigate the impact of diabetic retinopathy (DR) on morphological choriocapillaris (CC) modifications in eyes with type 1 macular neovascularization (MNV) secondary to AMD using optical coherence tomography angiography (OCTA). Methods: Eyes with AMD-related type 1 MNV with and without DR were prospectively included. We performed 3 × 3 mm OCTA scans at two visits: before the loading phase of intravitreal injections of aflibercept (T1) and 1 month after the last injection (T2). OCTA En face flow images of the CC were analyzed for flow deficit percentage (FD%), FD average area and FD number in a 500-µm-wide ring surrounding the dark halo (DH) around type 1 MNV. Results: A total of 65 eyes, out of which 30 eyes had mild DR, were included. In the group without diabetes, there was a gradual reduction in FD% in the CC ring around the DH after antiangiogenic therapy, indicating reperfusion of the CC (P = 0.003). However, in the DR group, there were no significant changes in CC parameters between the two study visits. Specifically, the FD% in the CC ring around the DH did not show a significant reduction at T2 compared with T1 values (P > 0.05). Furthermore, the comparison of the variation in FD% between the two groups was statistically significant. The nondiabetic group exhibited a gradual CC reperfusion after the loading phase of aflibercept, whereas the diabetic eyes did not show significant changes (P = 0.029). Conclusions: The CC surrounding the DH associated to type 1 MNV exhibited greater hypoperfusion in diabetic eyes compared with eyes without diabetes, both before starting therapy and after the loading phase. Hence, DR may be a potential risk factor in the development and progression of late-stage AMD and may also influence the response to antiangiogenic therapy.

Immediate effect of anti-VEGF injections on optic nerve head: Correlation between intraocular pressure and anatomical peripapillary changes.

PURPOSE: This study was designed to investigate retinal nerve fiber layer (RNFL) and radial peripapillary capillaries (RPC) changes on optical coherence tomography (OCT) angiography and OCT thickness alterations associated with acutely increased intraocular pressure after intravitreal injections. METHODS: This observational clinical study was conducted on 35 eyes (35 patients) with treatment-naïve age-related macular degeneration (AMD) and type 1 or type 2 MNV were enrolled. All patients underwent anti-vascular endothelial grow factor (VEGF) intravitreal injections with 0.05-mL aflibercept (2 mg) between January 2022 and October 2022. Peripapillary OCT angiography perfusion density, retinal nerve fiber layer thickness, and intraocular pressure (IOP) were measured before and immediately after intravitreal injections. In particular, the analysis was performed at the following visits: (T0) 5 to 15 min before the injection of aflibercept; (T1) 2 to 5 min after the injection of aflibercept. Paired t-test was used to compare pre-injection and post-injection values. RESULTS: The mean baseline IOP (T0) value was 17.26 ± 2.4 mmHg and the immediate post-injection IOP (T1) mean value was 34.7 ± 11.50 mmHg (P < 0.01). The mean global RNFL thickness before and immediately after the injection was 100.9 ± 18.8 m and 98.6 ± 17.4 m (P = 0.001). Furthermore, the topographical RNFL analysis showed significant thickness reduction of the nasal and inferior sectors after the procedure when compared to T0 (P = 0.046 and P = 0.001). On the contrary, the mean RCP density changes at T1 did not reach statistically significant (P = 0.636). Furthermore, we found a significant negative correlation between the retinal nerve fiber layer global thickness and the IOP changes (Pearson's correlation = -0.126; P = 0.031). In particular, the nasal RNFL region showed a significant negative correlations with IOP values (Pearson's correlation = -0.198, P = 0,046). CONCLUSIONS: We reported acute IOP changes that are associated with reduced RNFL thickness in a group of patients undergoing intravitreal injections of anti-VEGF drugs for neovascular age-related macular degeneration. Moreover, topographical sub-analysis revealed that the nasal RNFL region is most prone to IOP fluctuations. This finding may explain the sudden visual acuity change in patients immediately after injection and may sustain injuries to optic nerve head structures producing glaucomatous damage.

Choriocapillaris Reperfusion in Resolved Chronic Central Serous Chorioretinopathy Treated with Eplerenone: Long-Term Effects on the Fellow Eye.

INTRODUCTION: The aim of this work is to utilize swept-source optical coherence tomography angiography (SS-OCTA) to assess the long-term changes in the choroidal and choriocapillaris (CC) layers of the fellow unaffected eye of patients with unilateral resolved chronic central serous chorioretinopathy (cCSC) following treatment with continuous oral eplerenone (EPL). METHODS: The study included 35 patients with cCSC and subretinal fluid (SRF) in one eye. SS-OCTA imaging was performed on the fellow cCSC eyes at baseline, 6 months, and 12 months during eplerenone therapy. CC OCT angiography was analyzed to determine the percentage of choriocapillaris flow deficits (FD%), the number of flow deficits (FDn), and the average area of flow deficits (FDa). RESULTS: The results demonstrated significant changes in CC flow deficits from baseline to follow-up visits. Specifically, there was a significant decrease in FD% from 28.9 ± 2.2% at baseline to 26.4 ± 1.9% at 6 months (p = 0.023), and further to 24.9 ± 1.7% at 12 months (p = 0.001). Additionally, the FD area gradually contracted over the follow-up period (p < 0.05). Conversely, there was a significant increase in the number of flow deficits compared to baseline (p < 0.05). No statistically significant changes were observed in best-corrected visual acuity (BCVA) at the follow-up visits (p > 0.05). CONCLUSIONS: The findings of this study demonstrated long-term reperfusion of the choriocapillaris in unaffected fellow cCSC eyes during continuous oral eplerenone therapy. The beneficial effects of eplerenone therapy were observed after 6 months and maintained at 1 year. These results suggest that specific mineralocorticoid receptor (MR) antagonists may be effective in promoting choriocapillaris recovery in the unaffected eyes of patients with cCSC.

The Effectiveness of Paracetamol to Reduce the Post-Vaccination SARS-CoV-2 Adverse Effects in an Italian Vaccination Center.

The arrival of specific vaccines was crucial for the eradication of COVID-19. Despite the security of the vaccination, the administration of COVID-19 mRNA vaccines often causes systemic side effects for a short time after the injection, such as headache, fatigue, fever, muscle pain and nausea. These side effects can limit the adherence to COVID-19 vaccines administration, especially in healthcare workers. This study aims to analyze the impact of the prophylactic use of paracetamol to reduce the post-vaccination Comirnaty/Pfizer adverse effects. The study took place at the San Giovanni Battista Hospital in Rome and included all hospital employees who received two doses of Pfizer-BioNTech. The vaccination health personnel recommended the preventive intake of 1 g of paracetamol before the inoculation of the vaccine and then every 6 h in the first 24 h. Information was collected through forms and subsequent telephone recall. A total of 403 volunteers were involved in the study, with 391 of them receiving two doses and twelve individuals only one dose of the vaccine. The main results demonstrated that the prophylactic therapy influenced the lower onset of asthenia in the first and second doses. However, there were no significant differences between the two groups in terms of fever, headache and localized pain. Paracetamol had a good impact on the side effect of COVID-19 vaccination, reducing asthenia in both doses and mitigating the total of symptoms during the second vaccination.

Effects of diabetic retinopathy on longitudinal morphological changes in AMD-associated type 1 macular neovascularization.

The purpose of this study was to investigate the effect of diabetic retinopathy (DR) on longitudinal morphological changes in AMD-associated type 1 macular neovascularization using optical coherence tomography angiography (OCTA). We enrolled fifty treatment-naïve eyes with a diagnosis of exudative AMD and type 1 MNV. Twenty of 50 eyes were affected by mild DR. En face OCT angiography were examined for the MNV lesion area (mm2), the MNV flow area (mm2), the central macular thickness (CMT) and the BCVA. The OCTA acquisition was performed at the following visits: (i) before the loading phase (LP) of intravitreal injection of aflibercept (T1), and (ii) 1 month after the last intravitreal injection of loading phase comprising 3 monthly injections (T2). All morpho-functional parameters showed a significantly change at T2 compared to T1 values in both groups. Furthermore, we found a greater MNV area reduction after LP in eyes without DR (P = 0.023). With regard to the remaining parameters, no significant changes were found between two groups (P > 0.05). Our analysis revealed a less MNV area reduction after loading dose of anti-VEGF therapy in eyes affected by diabetic retinopathy.

Epidemiological and molecular evidence of intrafamilial transmission through sexual and vertical routes in Bahia, the state with the highest prevalence of HTLV-1 in Brazil.

INTRODUCTION: Familial clustering of HTLV-1 and related diseases has been reported in Brazil. However, intrafamilial transmission of HTLV-1 based on molecular analysis has been studied only in a few communities of Japanese immigrants and African-Brazilians. OBJECTIVE: To investigate the familial clustering of HTLV-1 infection and to determine the likely routes of transmission through epidemiological and genetic analyzes. METHODS: Medical records of 1,759 HTLV-1+ patients from de the Center for HTLV in Salvador, Brazil, were evaluated to identify first-degree relatives previously tested for HTLV-1. Familial clustering was assumed if more than one member of the same family was HTLV-1+. LTR regions of HTLV-1 sequences were analyzed for the presence of intrafamilial polymorphisms. Family pedigrees were constructed and analyzed to infer the likely transmission routes of HTLV-1. RESULTS: In 154 patients at least one other family member had tested positive for HTLV-1 (a total of 182 first-degree relatives). Of the 91 couples (182 individuals), 51.6% were breastfed, and 67.4% reported never using a condom. Of the 42 mother-child pairs, 23.8% had a child aged 13 years or younger; all mothers reported breastfeeding their babies. Pedigrees of families with 4 or more members suggests that vertical transmission is a likely mode of transmission in three families. Three families may have had both vertical and sexual transmission routes for HTLV-1. The genetic signatures of the LTR region of 8 families revealed 3 families with evidence of vertical transmission, another 3 families (spouses) with sexual transmission, and one family with both transmission routes. HTLV-1 sequences belonged to Cosmopolitan subtype HTLV-1a Transcontinental subgroup A. CONCLUSION: Sexual and vertical transmission routes contribute to the intrafamilial spread of HTLV-1 in the state of Bahia.

High seroprevalence of Leishmania infantum is linked to immune activation in people with HIV: a two-stage cross-sectional study in Bahia, Brazil.

Visceral leishmaniasis is an opportunistic disease in HIV-1 infected individuals, unrecognized as a determining factor for AIDS diagnosis. The growing geographical overlap of HIV-1 and Leishmania infections is an emerging challenge worldwide, as co-infection increases morbidity and mortality for both infections. Here, we determined the prevalence of people living with HIV (PWH) with a previous or ongoing infection by Leishmania infantum and investigated the virological and immunological factors associated with co-infection. We adopted a two-stage cross-sectional cohort (CSC) design (CSC-I, n = 5,346 and CSC-II, n = 317) of treatment-naïve HIV-1-infected individuals in Bahia, Brazil. In CSC-I, samples collected between 1998 and 2013 were used for serological screening for leishmaniasis by an in-house Enzyme-Linked Immunosorbent Assay (ELISA) with SLA (Soluble Leishmania infantum Antigen), resulting in a prevalence of previous or ongoing infection of 16.27%. Next, 317 PWH were prospectively recruited from July 2014 to December 2015 with the collection of sociodemographic and clinical data. Serological validation by two different immunoassays confirmed a prevalence of 15.46 and 8.20% by anti-SLA, and anti-HSP70 serology, respectively, whereas 4.73% were double-positive (DP). Stratification of these 317 individuals in DP and double-negative (DN) revealed a significant reduction of CD4+ counts and CD4+/CD8+ ratios and a tendency of increased viral load in the DP group, as compared to DN. No statistical differences in HIV-1 subtype distribution were observed between the two groups. However, we found a significant increase of CXCL10 (p = 0.0076) and a tendency of increased CXCL9 (p = 0.061) in individuals with DP serology, demonstrating intensified immune activation in this group. These findings were corroborated at the transcriptome level in independent Leishmania- and HIV-1-infected cohorts (Swiss HIV Cohort and Piaui Northeast Brazil Cohort), indicating that CXCL10 transcripts are shared by the IFN-dominated immune activation gene signatures of both pathogens and positively correlated to viral load in untreated PWH. This study demonstrated a high prevalence of PWH with L. infantum seropositivity in Bahia, Brazil, linked to IFN-mediated immune activation and a significant decrease in CD4+ levels. Our results highlight the urgent need to increase awareness and define public health strategies for the management and prevention of HIV-1 and L. infantum co-infection.

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.

Continuous Eplerenone Treatment in Chronic Central Serous Chorioretinopathy: Long-Term Results from a Pilot Study.

Purpose: To assess the long-term morpho-functional retinal and choroidal changes in chronic central serous chorioretinopathy (cCSC) pachychoroid eyes in response to continuous oral eplerenone (EPL) treatment. Methods: This pilot study was conducted on patients with unilateral exudative cCSC. We enrolled a total of 17 exudative cCSC and 17 non-exudative fellow eyes of 17 patients. Baseline best-corrected visual acuity (BCVA) and anatomical (structural optical coherence tomography [OCT] and OCT angiography) parameters in both eyes were collected at baseline. Follow-up data were collected at 6, 12, and 48 months after initiation of EPL treatment. Results: (i) Exudative cCSC eyes: Compared with baseline (0.34±0.13 LogMAR), BCVA significantly improved at follow-up examinations (6 months: 0.28±0.13 LogMAR, p=0.039; 12 months: 0.22±0.11 LogMAR, p=0.025; 48 months: 0.21±0.08 LogMAR, p=0.028). Furthermore, there was a significant reduction from baseline in all structural OCT parameters (subretinal fluid and subfoveal choroidal thickness [SFCT]; p<0.05). (ii) Non-exudative fellow eyes: There was no significant change in BCVA. There was a significant reduction from baseline in SFCT and choriocapillaris flow deficit percentage (p<0.05). Conclusion: In this pilot study, continuous oral EPL therapy in cCSC pachychoroid eyes resulted in long-term morpho-functional improvement. The beneficial effect of EPL occurred within the first year and was maintained after four years. Based on these preliminary observations, EPL may be effective in the exudative forms of CSC.

HTLV-1 Proviral Load in Vaginal Fluid Correlates with Levels in Peripheral Blood Mononuclear Cells.

BACKGROUND: The prevalence of human T-lymphotropic virus type-1 (HTLV-1) infection is higher in women, and sexual intercourse has been described as an important route of male-to-female transmission. The present study aimed to quantify HTLV-1 proviral load (PVL) in vaginal fluid, and to investigate correlations with PVL in peripheral blood mononuclear cells (PBMCs). In addition, cytopathological alterations and vaginal microbiota were evaluated. METHODS: HTLV-1-infected women were consecutively recruited at a multidisciplinary center for HTLV patients in Salvador, Brazil. All women underwent gynecological examinations to obtain cervicovaginal fluid and venipuncture for blood collection. PVL, as measured by real-time quantitative polymerase chain reaction (RT-qPCR), was expressed as the number of copies of HTLV-1/106 cells in blood and vaginal fluid samples. Light microscopy was used to assess cervicovaginal cytopathology and vaginal microbiota. RESULTS: In the 56 included women (43 asymptomatic carriers and 13 diagnosed with HTLV-1-associated myelopathy/tropical spastic paraparesis-HAM/TSP), mean age was 35.9 (SD ± 7.2) years. PVL was higher in PBMCs (median: 23,264 copies/106 cells; IQR: 6776-60,036) than in vaginal fluid (451.9 copies/106 cells; IQR: 0-2490) (p < 0.0001). PVL in PBMCs was observed to correlate directly with PVL in vaginal fluid (R = 0.37, p = 0.006). PVL was detected in the vaginal fluid of 24 of 43 (55.8%) asymptomatic women compared to 12 of 13 (92.3%) HAM/TSP patients, p = 0.02. Cytopathologic analyses revealed no differences between women with detectable or undetectable PVL. CONCLUSION: HTLV-1 proviral load is detectable in vaginal fluid and correlates directly with proviral load in peripheral blood. This finding suggests that sexual transmission of HTLV-1 from females to males may occur, as well as vertical transmission, particularly in the context of vaginal delivery.

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$11 415 per quality-adjusted life-year (QALY). 88% of all probabilistic sensitivity analysis simulations had ICER values lower than the Brazilian cost-effectiveness 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. FUNDING: None. TRANSLATIONS: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

Vaginal dryness in women infected by human T-lymphotropic virus type 1: an exploratory study.

Background: Human T-lymphotropic virus type-1 (HTLV-1) causes a variety of sicca symptoms, including xeroderma, xerostomia, and xerophthalmia. Aim: We sought to evaluate vaginal dryness via the degree of perceived vaginal lubrication, vaginal hormonal cytology, and direct measurements of vaginal wetting. Methods: The research was designed as a cross-sectional study. Vaginal dryness was assessed by scores in the lubrication domain of the Female Sexual Function Index (FSFI) questionnaire and the Vaginal Maturation Index (VMI) determined by vaginal hormonal cytology, as well as the measurement of vaginal lubrication using Schirmer strips placed at the anterior vaginal wall. Medians (25th-75th percentiles) were calculated for each group and compared using a nonparametric Kruskal-Wallis test and the Dunn-Bonferroni post hoc method. Outcomes: Outcomes were detection of the presence of vaginal dryness in women who were infected or noninfected with HTLV-1. Results: HTLV-1-infected women (n = 72, 57 asymptomatic and 15 with HTLV-1-associated myelopathy/tropical spastic paraparesis [HAM/TSP]) and uninfected women (n = 49) were studied. Women with HAM/TSP had significantly lower FSFI lubrication scores than asymptomatic and uninfected women (P = .032). In addition, women with HAM/TSP had significantly lower VMI compared with the asymptomatic and uninfected groups (P = .027 and P = .039, respectively). Clinical Implications: The results of this study show a reduction in vaginal lubrication in HTLV-1-infected women diagnosed with HAM/TSP compared with asymptomatic and uninfected women. Strengths and Limitations: The lack of a gold standard test for the diagnosis of vaginal dryness and the fact that no assessment of vaginal pH was performed were limitations of this study. The strength of the study was the comprehensive assessment of vaginal dryness from several perspectives: subjective (perception of vaginal lubrication according to the vaginal lubrication domain of the FSFI), hormonal (vaginal hormonal cytology to assess local hormone status), and the degree of vaginal moisture (direct measurement of vaginal dryness with an instrument, the Schirmer strip, already used to measure the presence of dry eye). Conclusion: HTLV-1-infected women with HAM/TSP have decreased vaginal lubrication compared with asymptomatic and uninfected women after adjusting for age.

Sodium intake and urinary losses in children on dialysis: a European multicenter prospective study.

BACKGROUND: Sodium (Na) balance is unexplored in dialyzed children. We assessed a simplified sodium balance (sNaB) and its correlates in pediatric patients receiving maintenance dialysis. METHODS: Patients < 18 years old on hemodialysis (HD) or peritoneal dialysis (PD) in six European Pediatric Dialysis Working Group centers were recruited. sNaB was calculated from enteral Na, obtained by a 3-day diet diary, Na intake from medications, and 24-h urinary Na (uNa). Primary outcomes were systolic blood pressure and diastolic blood pressure standard deviation scores (SBP and DBP SDS), obtained by 24-h ambulatory blood pressure monitoring or office BP according to age, and interdialytic weight gain (IDWG). RESULTS: Forty-one patients (31 HD), with a median age of 13.3 (IQR 5.2) years, were enrolled. Twelve patients (29.3%) received Na-containing drugs, accounting for 0.6 (0.7) mEq/kg/day. Median total Na intake was 1.5 (1.1) mEq/kg/day, corresponding to 60.6% of the maximum recommended daily intake for healthy children. Median uNa and sNaB were 0.6 (1.8) mEq/kg/day and 0.9 (1.7) mEq/kg/day, respectively. The strongest independent predictor of sNaB in the cohort was urine output. In patients receiving HD, sNaB correlated with IDWG, pre-HD DBP, and first-hour refill index, a volume index based on blood volume monitoring. sNaB was the strongest predictor of IDWG in multiple regression analysis (ß = 0.63; p = 0.005). Neither SBP SDS nor DBP SDS correlated with sNaB. CONCLUSIONS: Na intake is higher than uNa in children on dialysis, and medications may be an important source of Na. sNaB is best predicted by urine output in the population, and it is a significant independent predictor of IDWG in children on HD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Short-term peripapillary structural and vascular changes following anti-VEGF vs. Dexamethasone intravitreal therapy in patients with DME.

PURPOSE: To evaluate short-term peripapillary structural and vascular changes in DME after treatment with dexamethasone implant (DEX-I) and anti-VEGFs using OCT-A. METHODS: Sixty-five patients with naïve center-involving DME were enrolled. 33 of sixty five patients (group 1) underwent with single DEX-I 0.7 mg (Ozurdex, Allergan, Inc., USA), 32 of sixty-five (group 2) underwent with intravitreal injection of aflibercept 0.5 mg (Eylea, Bayer, Genentech, San Francisco, USA). The OCT acquisition was completed at the following visits: (i) "T1 visit" corresponding to the intravitreal injection of DEX-I or aflibercept in patients with naïve center-involving DME (ii) "T2 visit" corresponding to the examination performed 2 weeks after intravitreal injection of aflibercept and 1 month after DEX-I. The parameters analyzed were: (i) RPC vasculature density (VD); (ii) peripapillary retinal nerve fiber layer (pRNFL) thickness, and (iii) intraocular pressure (IOP). RESULTS: The RPC analysis showed a VD increase at T2 in both groups, although values did not reach statistical significance (48.12± 4.17 and 49.04 ± 4.23; P = 0.081 in Group 1 and 46.93± 3.16 and 47.17 ± 3.70; P = 0.087 in Group 2). Likewise, the pRNFL thickness and IOP fluctuations did not show statistically significant changes in in both groups among the different study visits. CONCLUSIONS: After intravitreal injection (anti-VEGF or DEX-I), no significant short-term changes were found in peripapillary microvasculature, IOP and pRNFL thickness in diabetic eyes treated with anti-VEGF or DEX-I.