Multi-center Integrating Radiomics, Structured Reports, and Machine Learning Algorithms for Assisted Classification of COVID-19 in Lung Computed Tomography.

Purpose: To evaluate the classification performance of structured report features, radiomics, and machine learning (ML) models to differentiate between Coronavirus Disease 2019 (COVID-19) and other types of pneumonia using chest computed tomography (CT) scans. Methods: Sixty-four COVID-19 subjects and 64 subjects with non-COVID-19 pneumonia were selected. The data was split into two independent cohorts: one for the structured report, radiomic feature selection and model building (n = 73), and another for model validation (n = 55). Physicians performed readings with and without machine learning support. The model's sensitivity and specificity were calculated, and inter-rater reliability was assessed using Cohen's Kappa agreement coefficient. Results: Physicians performed with mean sensitivity and specificity of 83.4 and 64.3%, respectively. When assisted with machine learning, the mean sensitivity and specificity increased to 87.1 and 91.1%, respectively. In addition, machine learning improved the inter-rater reliability from moderate to substantial. Conclusion: Integrating structured reports and radiomics promises assisted classification of COVID-19 in CT chest scans.

Evidence against Zika virus infection of pets and peri-domestic animals in Latin America and Africa.

Decades after its discovery in East Africa, Zika virus (ZIKV) emerged in Brazil in 2013 and infected millions of people during intense urban transmission. Whether vertebrates other than humans are involved in ZIKV transmission cycles remained unclear. Here, we investigate the role of different animals as ZIKV reservoirs by testing 1723 sera of pets, peri-domestic animals and African non-human primates (NHP) sampled during 2013-2018 in Brazil and 2006-2016 in Côte d'Ivoire. Exhaustive neutralization testing substantiated co-circulation of multiple flaviviruses and failed to confirm ZIKV infection in pets or peri-domestic animals in Côte d'Ivoire (n=259) and Brazil (n=1416). In contrast, ZIKV seroprevalence was 22.2% (2/9, 95% CI, 2.8-60.1) in West African chimpanzees (Pan troglodytes verus) and 11.1% (1/9, 95% CI, 0.3-48.3) in king colobus (Colobus polycomos). Our results indicate that while NHP may represent ZIKV reservoirs in Africa, pets or peri-domestic animals likely do not play a role in ZIKV transmission cycles.

Mutational spectrum of breast cancer susceptibility genes among women ascertained in a cancer risk clinic in Northeast Brazil.

PURPOSE: There is a paucity of data on the spectrum and prevalence of pathogenic variants among women of African ancestry in the Northeast region of Brazil. METHODS: We performed BROCA panel sequencing to identify inherited loss-of-function variants in breast cancer susceptibility genes among 292 Brazilian women referred to a single institution cancer risk assessment program. RESULTS: The study included a convenient cohort of 173 women with invasive breast cancer (cases) and 119 women who were cancer-free at the time of ascertainment. The majority of the women self-reported as African-descended (67% for cases and 90.8% for unaffected volunteers). Thirty-seven pathogenic variants were found in 36 (20.8%) patients. While the spectrum of pathogenic variants was heterogeneous, the majority (70.3%) of the pathogenic variants were detected in high-risk genes BRCA1, BRCA2, PALB2, and TP53. Pathogenic variants were also found in the ATM, BARD1, BRIP1, FAM175A, FANCM, NBN, and SLX4 genes in 6.4% of the affected women. Four recurrent pathogenic variants were detected in 11 patients of African ancestry. Only one unaffected woman had a pathogenic variant in the RAD51C gene. Different risk assessment models examined performed well in predicting risk of carrying germline loss-of-function variants in BRCA1 and/or BRCA2 in breast cancer cases. CONCLUSION: The high prevalence and heterogenous spectrum of pathogenic variants identified among self-reported African descendants in Northeast Brazil is consistent with studies in other African ancestry populations with a high burden of aggressive young onset breast cancer. It underscores the need to integrate comprehensive cancer risk assessment and genomic testing in the management of newly diagnosed Black women with breast cancer across the African Diaspora, enabling improved cancer control in admixed underserved and understudied populations.

Technical note: Partitioning of gated single photon emission computed tomography raw data for protocols optimization.

PURPOSE: Methodologies for optimization of SPECT image acquisition can be challenging due to imaging throughput, physiological bias, and patient comfort constraints. We evaluated a vendor-independent method for simulating lower count image acquisitions. METHODS: We developed an algorithm that recombines the ECG-gated raw data into reduced counting acquisitions. We then tested the algorithm to simulate reduction of counting statistics from phantom SPECT image acquisition, which was synchronized with an ECG simulator. The datasets were reconstructed with a resolution recovery algorithm and the summed stress score (SSS) was assessed by three readers (two experts and one automatic). RESULTS: The algorithm generated varying counting levels, simulating multiple examinations at the same time. The error between the expected and the simulated countings ranged from approximately 5% to 10% for the ungated simulations and 0% for the gated simulations. CONCLUSIONS: The vendor-independent algorithm successfully generated lower counting statistics datasets from single-gated SPECT raw data. This method can be readily implemented for optimal SPECT research aiming to lower the injected activity and/ or to shorten the acquisition time.

Ecologic Determinants of West Nile Virus Seroprevalence among Equids, Brazil.

Among 713 equids sampled in northeastern Brazil during 2013-2018, West Nile virus seroprevalence was 4.5% (95% CI 3.1%-6.3%). Mathematical modeling substantiated higher seroprevalence adjacent to an avian migratory route and in areas characterized by forest loss, implying increased risk for zoonotic infections in disturbed areas.

Early and Successful Combination Antiretroviral Therapy Normalizes Survival Time in Patients Coinfected With Human Immunodeficiency Virus and Human T-cell Lymphotrophic Virus Type 1.

BACKGROUND: Coinfection with human T-cell lymphotrophic virus type 1 (HTLV-1) is associated with shorter survival for adults and children infected with human immunodeficiency virus (HIV), although the reasons remain a matter of debate. We evaluated the factors associated with survival time in a large cohort of HIV/HTLV-1-coinfected and HIV-monoinfected individuals on combination antiretroviral therapy (cART). METHODS: In a nested, retrospective case-control study (1:1), we reviewed medical records of people with HIV infection on cART in a referral AIDS center in Salvador, Brazil. We matched 149 patients coinfected with HTLV-1 (cases) by age at HIV diagnosis and sex, to an equal number of HTLV-uninfected persons (controls). Death rates, survival time, baseline and current CD4 cell count, last HIV-1 RNA plasma viral load (pVL), and causes of death were compared between groups. RESULTS: The overall mortality rate was 2.1 person-years (76 deaths, 53 among coinfected patients). Survival time for cases (16.7 ± 0.7 years) was significantly shorter than for controls (18.1 ± 0.4 years; P = .001). Among patients with pVL >50 copies/mL, coinfected patients had a shorter survival time (8.4 ± 0.8 years) than monoinfected ones (12.9 ± 1.4 years; P = .02), regardless of pVL magnitude. However, survival time did not differ for HIV-monoinfected (19.0 ± 0.4 years) or coinfected patients (20.2 ± 0.6 years) presenting with pVL <50 copies/mL (P = .5). Deceased coinfected patients had higher initial CD4 count (417 ± 219 cells) than monoinfected ones with the same outcome (177 ± 160 cells; P = .004), while survivors had similar CD4 cell count at baseline, regardless of HTLV status. CONCLUSIONS: Successful cART is able to normalize survival for coinfected patients and should be introduced for all coinfected patients, regardless of CD4 cell count.HIV/human T-cell lymphotrophic virus type 1 coinfection is believed to decrease survival of coinfected patients. In this case-control study, we demonstrate that successful combination antiretroviral therapy (last HIV viral load <50 copies/mL) is able to improve survival of coinfected patients to levels observed for those monoinfected.

Rapid decline of Zika virus NS1 antigen-specific antibody responses, northeastern Brazil.

Zika virus (ZIKV) is a positive-stranded RNA virus within the Flaviviridae family. After decades of circulation in Asia, ZIKV was introduced to Brazil in 2014-2015, associated with a rise in congenital malformations. Unlike the genetically related dengue virus (DENV), ZIKV constitutes only one serotype. Although assumed that ZIKV infection may engender lifelong immunity, the long-term kinetics of ZIKV antibody responses are unclear. We assessed long-term kinetics of ZIKV NS1-IgG response in 144 individuals from 3 different subpopulations: HIV patients, tuberculosis patients and healthy individuals first tested in 2016 and retested 1.5-2 years after the 2015-2016 ZIKV epidemic in Salvador de Bahia, Brazil, using a widely distributed NS1-based commercial ELISA. The seropositivity in 2016 reached 59.0% (85/144, 95% confidence interval (CI) 50.7-66.7%), and decreased to 38.6% (56/144, CI 31.3-47.0%) 1.5-2 years later. In addition, the median ZIKV NS1-ELISA reactivity for individuals that remained positive in both timepoints significantly decreased from a ratio of 4.4 (95% CI 3.8-5.0) to 1.6 (95% CI 1.6-1.9) over the 2-year interval (Z: - 6.1; p < 0.001) irrespective of the subpopulation analyzed. Initial 2016 DENV antibody response was non-significant between groups, suggesting comparable DENV background. The high 20.6% seroreversion suggest that widely used serologic tests may fail to account a considerable proportion of past ZIKV infections in flavivirus endemic countries. In addition, ZIKV immunity might be shorter-lived than previously thought, which may contribute to local ZIKV resurgence once individual immune responses wane sufficiently to reduce community protective immunity in addition to birth and migration.

Comparison of Three Health-Related Quality of Life Instruments to Evaluate Symptoms of Depression in HIV Patients in Brazil.

The evaluation of quality of life could be a useful indicator of depression in HIV patients. We compared the performance of three health-related quality of life (HRQoL) instruments for detecting depression. This nested case-control study included 200 HIV patients attended at an AIDS referral center. Depression was measured by Beck Depression Inventory (BDI). We accessed HRQoL by SF-36v2, HAT-QoL, and WHOQOL-HIV Bref. The depression diagnostic accuracy was evaluated by receiver operating characteristic (ROC) curve analysis. SF-36v2 presented negative correlation with BDI score (- 0.72 to - 0.40), and HAT-QoL (- 0.66 to 0.05) and WHOQoL-HIV Bref (- 0.67 to 0.32) domains presented negative and positive correlations. Mental Health (r = - .71) and Mental Component Summary (r = - .72) showed high negative correlation with BDI. SF-36v2 showed excellent measure by the ROC curve analysis in four factors, and high correlation in Mental Health and MCS. Sf-36 may represent a useful tool for screening of depressive symptoms in HIV patients.

Label-free quantitative mass spectrometry from formalin-fixed paraffin-embedded samples of nasopharyngeal carcinoma: Preliminary results from a non-endemic European cohort of patients.

AIM: Report our results of biomarker discovery in formalin-fixed paraffin-embedded (FFPE) nasopharyngeal carcinoma (NPC) via proteomic analysis. BACKGROUND: Nasopharyngeal carcinoma (NPC) is a rare cancer in Western countries. Proteomic analysis have already been reported as a useful tool to provide biomarkers. Formalin-fixed paraffin-embedded (FFPE) samples, despite largely underused, can provide invaluable information for biomarker research via proteomic analysis. METHODS: FFPE samples of NPC were submitted to protein extraction followed by FASP-digestion and label-free quantitative mass spectrometry (MS). Patients' received concurrent chemoradiation with or without adjuvant chemotherapy as per Intergroup 0099 trial. IMRT was delivered following the RTOG0615 specifications. Toxicity was scored using the CTCAE 4.03 tables. Survival was estimated using Kaplan-Meier curves. Log-rank was used to detect differences. KEGG ontology graphics were generated. RESULTS: 28 FFPE samples from NPC patients were used. Patients were: 79% male, 97% Caucasians, 86% WHO type 3, 40% T1, 10% T2, 25% T3, and 25% T4. With a median follow up of 37 months, local control was 83 (T1, 100% T2, T3 and T4), overall survival was 84%, and six patients developed distant metastases. All five patients that died were due to metastatic disease. Tumor samples contained a median of 75% of tumor material. We found Epstein-Barr (EBV) and Herpes simplex (HSV) viruses' related proteins significantly present in early-stage primary NPC (T1 and T2, p < 0.01). A pool of 10 proteins was statistically up-regulated in the metastatic group of patients (p < 0.01). Median survival from this M1 group was <1 year (p < 0.001). CONCLUSIONS: FFPE samples yielded adequate material for MS analysis. We found EBV and HSV related proteins on early-stage NPC, and proteomic profiling associated with distant metastases, potential candidates of disease biomarkers. Validation is needed.

Surgery versus radiotherapy: Long term outcomes of T1 glottic cancer.

AIM: The aim of this study was to compare the outcomes, patterns of failure and laryngeal preservation rates in patients with T1N0 glottic cancer treated with surgery or radiotherapy. MATERIALS/METHODS: Retrospective study of T1N0 glottic cancer patients treated in our institution between January 2007 and December 2017. Histologically proven squamous cell carcinoma patients, treated with upfront cordectomy/partial laryngectomy (S group) or radiotherapy (RT group) were included. Elective treatment of the neck was not permitted. Local failure (LF), disease-free survival (DFS), ultimate disease-free survival (UDFS), laryngectomy-free survival (LFS), disease-specific mortality (DSM) and overall survival (OS) were evaluated. RESULTS: Two hundred and one patients were eligible (172 S group, 29 RT group), with a median follow-up of 38.8 months. Overall, 33 (16%) patients had a recurrence, 30 (17%) in the S group and 3 (10%) in the RT group. Local failure was the predominant site of failure (28 S, 2 RT). Overall, of all those that were salvaged, 17 (8%) underwent total laryngectomy (15 S, 2 RT). There was no significant difference in the 5-year cumulative incidence of LF (20.8% S, 8.1% RT, p = 0.138), 5-y LFS (85.0% vs. 91.7%, p = 0.809), 5-y DFS (67.5% vs. 82.1%, p = 0.343), 5-y UDFS (82.5% vs. 90.3%, p = 0.647) and 5-y OS (84.5% vs. 90.3%, p = 0.892). Multivariate analysis showed no correlation between initial treatment and the analyzed outcomes. CONCLUSION: Primary surgery or radiotherapy were similar first line options, since they do not differ in all outcomes. Patients' and physician's preferences must be considered when choosing first treatment.

Improved long-term results of intensity-modulated radiotherapy for a non-endemic European nasopharyngeal carcinoma cohort: single-center retrospective study.

PURPOSE: Report our matured outcomes of European nasopharyngeal carcinoma (NPC) treatment from a non-endemic region in the IMRT era. METHODS: We reviewed 109 consecutive patients with biopsy proven NPC treated between 2009 and 2013. All received IMRT as per RTOG 0615. Toxicity was scored accordingly to CTCAE 4.03. Platinum-based chemotherapy was delivered following the Intergroup 0099. RESULTS: Median age of 53 years; 97% Caucasian; 74% male; 72% WHO grade III; 43% T1; 14% T2; 18% T3, 25% T4; 17% N0; 17% N1; 39% N2; 27% N3. Compliance to adjuvant chemotherapy was 88%. With a median follow up of 56 months, the 4-year local control was 90.2% (88.6% for T1; 100% for T2; 85% for T3; and 91.7% for T4), the 4-year distant metastases-free survival was 86% and an overall survival rate was 77%. Local control and survival were better in G3 (p < 0.001 and p = 0.032, respectively). Xerostomia was the most frequent late toxicity in 55% (n = 60). Hypothyroidism requiring hormonal reposition occurred in 15.5% (n = 17). From the 36 deaths, 20 were due to distant metastases, 3 grade 5 toxicity, 2 from local progression, 5 non-cancer deaths and unknown cause in the remaining 6. On multivariable analysis, age (p = 0.017), local recurrence and distant metastases were associated with death (p < 0.001, both). CONCLUSION: Our matured data from the IMRT era showed a major improvement from our 3D cohort series reaching excellent local and regional control, even in T4. Local recurrences, despite few, and distant metastases were correlated with the risk of death.

Cross-Protection of Dengue Virus Infection against Congenital Zika Syndrome, Northeastern Brazil.

The Zika virus outbreak in Latin America resulted in congenital malformations, called congenital Zika syndrome (CZS). For unknown reasons, CZS incidence was highest in northeastern Brazil; one potential explanation is that dengue virus (DENV)-mediated immune enhancement may promote CZS development. In contrast, our analyses of historical DENV genomic data refuted the hypothesis that unique genome signatures for northeastern Brazil explain the uneven dispersion of CZS cases. To confirm our findings, we performed serotype-specific DENV neutralization tests in a case-control framework in northeastern Brazil among 29 Zika virus-seropositive mothers of neonates with CZS and 108 Zika virus-seropositive control mothers. Neutralization titers did not differ significantly between groups. In contrast, DENV seroprevalence and median number of neutralized serotypes were significantly lower among the mothers of neonates with CZS. Supported by model analyses, our results suggest that multitypic DENV infection may protect from, rather than enhance, development of CZS.

Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: the ZIKAlliance consortium.

BACKGROUND: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. METHODS: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmission clustering, disabilities and health economics, viral kinetics, the potential role of antibody enhancement, and co-infections will be linked to the cohort studies. DISCUSSION: Results of these large cohort studies will provide better risk estimates for birth defects and other developmental abnormalities associated with ZIKV infection including possible co-factors for the variability of risk estimates between other countries and regions. Additional outcomes include incidence and transmission estimates of ZIKV during and after pregnancy, characterization of short and long-term clinical course following infection and viral kinetics of ZIKV. STUDY REGISTRATIONS: clinicaltrials.gov NCT03188731 (PW cohort), June 15, 2017; clinicaltrials.gov NCT03393286 (CH cohort), January 8, 2018; clinicaltrials.gov NCT03204409 (NH cohort), July 2, 2017.

External Quality Assessment for Zika Virus Molecular Diagnostic Testing, Brazil.

We conducted an external quality assessment of Zika virus molecular diagnostic tests in Brazil using a new Zika virus standard. Of 15 laboratories, 73% showed limited sensitivity and specificity. Viral load estimates varied significantly. Continuous quality assurance is needed to adequately estimate risk for Zika virus-associated disease and determine patient care.

A novel hepatitis B virus species discovered in capuchin monkeys sheds new light on the evolution of primate hepadnaviruses.

BACKGROUND & AIMS: All known hepatitis B virus (HBV) genotypes occur in humans and hominoid Old World non-human primates (NHPs). The divergent woolly monkey HBV (WMHBV) forms another orthohepadnavirus species. The evolutionary origins of HBV are unclear. METHODS: We analysed sera from 124 Brazilian monkeys collected during 2012-2016 for hepadnaviruses using molecular and serological tools, and conducted evolutionary analyses. RESULTS: We identified a novel orthohepadnavirus species in capuchin monkeys (capuchin monkey hepatitis B virus [CMHBV]). We found CMHBV-specific antibodies in five animals and high CMHBV concentrations in one animal. Non-inflammatory, probably chronic infection was consistent with an intact preCore domain, low genetic variability, core deletions in deep sequencing, and no elevated liver enzymes. Cross-reactivity of antisera against surface antigens suggested antigenic relatedness of HBV, CMHBV, and WMHBV. Infection-determining CMHBV surface peptides bound to the human HBV receptor (human sodium taurocholate co-transporting polypeptide), but preferentially interacted with the capuchin monkey receptor homologue. CMHBV and WMHBV pseudotypes infected human hepatoma cells via the human sodium taurocholate co-transporting polypeptide, and were poorly neutralised by HBV vaccine-derived antibodies, suggesting that cross-species infections may be possible. Ancestral state reconstructions and sequence distance comparisons associated HBV with humans, whereas primate hepadnaviruses as a whole were projected to NHP ancestors. Co-phylogenetic analyses yielded evidence for co-speciation of hepadnaviruses and New World NHP. Bayesian hypothesis testing yielded strong support for an association of the HBV stem lineage with hominoid ancestors. Neither CMHBV nor WMHBV was likely the ancestor of the divergent human HBV genotypes F/H found in American natives. CONCLUSIONS: Our data suggest ancestral co-speciation of hepadnaviruses and NHP, and an Old World origin of the divergent HBV genotypes F/H. The identification of a novel primate hepadnavirus offers new perspectives for urgently needed animal models of chronic hepatitis B. LAY SUMMARY: The origins of HBV are unclear. The new orthohepadnavirus species from Brazilian capuchin monkeys resembled HBV in elicited infection patterns and could infect human liver cells using the same receptor as HBV. Evolutionary analyses suggested that primate HBV-related viruses might have emerged in African ancestors of New World monkeys millions of years ago. HBV was associated with hominoid primates, including humans and apes, suggesting evolutionary origins of HBV before the formation of modern humans. HBV genotypes found in American natives were divergent from those found in American monkeys, and likely introduced along prehistoric human migration. Our results elucidate the evolutionary origins and dispersal of primate HBV, identify a new orthohepadnavirus reservoir, and enable new perspectives for animal models of hepatitis B.

Oral health and health-related quality of life in HIV patients.

BACKGROUND: Oral health care may improve the health-related quality of life (HRQoL) of HIV/AIDS patients. We aimed to evaluate oral health and HRQoL of HIV/AIDS patients using antiretroviral therapy. METHODS: A cross-sectional study included 120 HIV-infected patients, aged ≥18 years, from February, 2016 to September, 2017. The 36-Item Short Form Health Survey (SF-36) was used to evaluate the HRQoL. We assessed dental caries status using the Decayed, Missing and Filled Teeth (DMFT) index. Information about demographic, socioeconomic status, depression, and other comorbidities were collected. All patients with depression had a medical diagnosis. Comorbidities were defined as medical diagnoses of arterial hypertension, type-2 diabetes, tuberculosis, syphilis, cardiopathy, chronic renal failure, lymphoma, HCV infection, HBV infection and fatty liver disease. Independent t-tests were used to compare differences between mean levels of HRQoL, age, and DMFT and its components according to groups of sex, comorbidities and depression. Simple linear regression was used to analyze the relationship between the Mental Component Summary (MCS) and DMFT, and a multiple regression equation investigated depression, age, MCS, and comorbidities as predictors of DMFT. RESULTS: The mean DMFT index was 12.4 ± 8.2. A linear regression equation estimated a significant (p = 0.022) decrease of 0.25 unit (%) in MCS for each unit increase in DMFT. Among depressed patients, a significant (p = 0.008) decrease of 0.67% in MCS for each unity increase in DMFT was estimated. Depressed patients showed worse oral health indicators (DFMT index; p ≤ 0.001; and mean Missing Teeth; p ≤ 0.052) and lower HRQoL domains than non-depressed patients. DMFT remained associated with depression (P < 0.005) after controlling for age, MCS, and comorbidities. CONCLUSIONS: We found association between poorer oral health (higher DMFT index) and lower Mental Health Component Summary in HIV-infected patients with depression. Patients with depression deserve especial attention to their HRQoL and oral care.

Evidence for Congenital Zika Virus Infection From Neutralizing Antibody Titers in Maternal Sera, Northeastern Brazil.

Reliable diagnosis of congenital Zika virus (ZIKV) infection is challenging. Here, we assessed ZIKV-specific neutralizing antibodies in 28 mothers of children with microcephaly (cases) and 122 controls from northeastern Brazil using plaque reduction neutralization tests. ZIKV-specific antibody titers were significantly higher in cases than in controls (t test, P < .0001). We identified a putative case of congenital Zika syndrome retrospectively by unusually high ZIKV-specific antibody titers. High ZIKV-specific antibody titers in cases were unrelated to prior dengue virus infection. Our data suggest a strong immunological stimulus from prolonged placental or transplacental ZIKV shedding and potential utility of maternal antibody titers to corroborate congenital ZIKV infection.

Increased expression of CD38 and HLADR in HIV-infected patients with oral lesion.

Persistent immune actiation is associated with innadequate immune recovery in HIV-patients. This study assessed the relationship between frequency of expression of cell activation markers (CD38 and HLADR) and presence of oral lesions in HIV-1 infected patients. Fifty-seven HIV-infected persons, undergoing antiretroviral treatment, were divided into three groups, according to the number of CD4+ T cells and CD4+ /CD8+ ratio: adequate, partial, and inadequate immune restauration. All patients underwent full mouth assessments for saliva flow measurement, oral mucosal lesion, periodontal disease, and severity of periodontitis. Immune activation markers levels were compared according to three groups of periodontal disease ("No periodontal disease," "gingivitis," and "periodontitis"). Oral mucosal lesions (P = 0.03) and peridodontal disease (P = 0.03) were associated with lower CD4+ /CD8+ ratio. Patients with oral mucosal lesions had significantly higher median levels of HLADR and CD38 markers in all T-lymphocytes populations than patients without oral lesions. Patients with gingivitis and with periodontitis presented significantly higher median levels of CD3+ HLADR+ , CD4+ HLADR+ , CD8+ HLADR+ , and CD3+ CD38+ and significantly lower CD4+ /CD8+ ratio than patients with no periodontal disease. Increased levels of HLADR and CD38 expressions in peripheral blood were associated with oral lesions in HIV-positive patients. Periodontal disease was associated with HLADR expression.

Tuberculosis incidence in a cohort of individuals infected with human T-lymphotropic virus type 1 (HTLV-1) in Salvador, Brazil.

BACKGROUND: Few reports have investigated the association between human T-lymphotropic virus type 1 (HTLV-1) and tuberculosis (TB) in countries where both infections are endemic. This study estimates the incidence of TB in a cohort infected with HTLV-1, compared with non-infected individuals, over a ten-year period. METHODS: Retrospective cohort study involving the cross-matching of records of individuals for whom a HTLV serology was performed at a referral center for HTLV (CHTLV) with a database of TB cases from Sinan-the Information System on Diseases of Compulsory Declaration between 2002 and 2012. RESULTS: From a cohort of 6,495 individuals, 1,711 were infected with HTLV-1. A total of 73 TB cases occurred during the study period: 33 HTLV-1-infected patients and 40 uninfected individuals. The incidence density for TB in the HTLV-1 infected group was 3.3 person-years per 1,000 individuals and 1.1 person-years per 1,000 individuals in the group HTLV-1 uninfected group. The relative risk of developing TB in the group of patients infected with HTLV-1 was 2.6 (CI 95 % 1.6-4.2) in comparison with HTLV-1 uninfected group. Compared to individuals with isolated TB, those in the HTLV-1 infected group who had TB were older (p = 0.005) and had lower education levels (p = 0.02). No differences were observed with respect to the clinical/radiological presentation, nor in the outcome of TB and prevalence of HIV infection, when comparing among the HTLV-1-infected and uninfected groups. CONCLUSIONS: Patients infected with HTLV-1 are more susceptible to TB. The epidemiological characteristics of HTLV-1/TB subjects and those infected with TB overlap.