Efficacy and Safety of Switching to the 2-Drug Regimen Dolutegravir/Lamivudine Versus Continuing a 3- or 4-Drug Regimen for Maintaining Virologic Suppression in Adults Living With Human Immunodeficiency Virus 1 (HIV-1): Week 48 Results From the Phase 3, Noninferiority SALSA Randomized Trial.

BACKGROUND: In TANGO, switching to dolutegravir/lamivudine (DTG/3TC) demonstrated long-term noninferior efficacy vs continuing tenofovir alafenamide-based regimens in treatment-experienced adults with HIV-1. The phase 3 SALSA study evaluated efficacy and safety of switching to DTG/3TC compared with continuing various 3-/4-drug current antiretroviral regimens (CARs). METHODS: Adults with HIV-1 RNA <50 copies/mL and no previous virologic failure were randomized (1:1, stratified by baseline third agent class) to switch to once-daily fixed-dose combination DTG/3TC or continue CAR (primary endpoint: proportion of participants with HIV-1 RNA ≥50 copies/mL at week 48; Snapshot, intention-to-treat-exposed population, 5% noninferiority margin). RESULTS: Overall, 493 adults (39% women; 39% aged ≥50 years; 19% African American/African heritage; 14% Asian) were randomized to switch to DTG/3TC (n = 246) or continue CAR (n = 247). At week 48, 1 (0.4%) participant in the DTG/3TC group and 3 (1.2%) in the CAR group had HIV-1 RNA ≥50 copies/mL (Snapshot), demonstrating noninferiority (adjusted difference, -0.8%; 95% CI, -2.4%, .8%). Zero participants met confirmed virologic withdrawal criteria; therefore, no resistance testing was performed. Drug-related adverse events were more frequent with DTG/3TC (20%) than CAR (6%) through week 48 but comparable post-week 24 (5% vs 2%, respectively). Proximal tubular renal function and bone turnover biomarkers improved with DTG/3TC. Both groups had generally minimal changes in lipids and inflammatory biomarkers. CONCLUSIONS: Switching to DTG/3TC was noninferior to continuing CAR for maintaining virologic suppression at week 48 with no observed resistance, supporting the efficacy, good safety, and high barrier to resistance of DTG/3TC. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov, NCT04021290.

Comparing the performance of dengue virus IgG and IgG-capture enzyme-linked immunosorbent assays in seroprevalence study.

BACKGROUND: Dengue virus (DENV) is the leading cause of arboviral diseases in humans worldwide. Currently Dengvaxia, the first dengue vaccine licensed in 20 countries, was recommended for DENV seropositive individuals aged 9-45 years. Studying dengue seroprevalence can improve our understanding of the epidemiology and transmission dynamics of DENV, and facilitate future intervention strategies and assessment of vaccine efficacy. Several DENV envelope protein-based serological tests including IgG and IgG-capture enzyme-linked immunosorbent assays (ELISAs) have been employed in seroprevalence studies. Previously DENV IgG-capture ELISA was reported to distinguish primary and secondary DENV infections during early convalescence, however, its performance over time and in seroprevalence study remains understudied. METHODS: In this study, we used well-documented neutralization test- or reverse-transcription-polymerase-chain reaction-confirmed serum/plasma samples including DENV-naïve, primary and secondary DENV, primary West Nile virus, primary Zika virus, and Zika with previous DENV infection panels to compare the performance of three ELISAs. RESULTS: The sensitivity of the InBios IgG ELISA was higher than that of InBios IgG-capture and SD IgG-capture ELISAs. The sensitivity of IgG-capture ELISAs was higher for secondary than primary DENV infection panel. Within the secondary DENV infection panel, the sensitivity of InBios IgG-capture ELISA decreased from 77.8% at < 6 months to 41.7% at 1-1.5 years, 28.6% at 2-15 years and 0% at > 20 years (p < 0.001, Cochran-Armitage test for trend), whereas that of IgG ELISA remains 100%. A similar trend was observed for SD IgG-capture ELISA. CONCLUSIONS: Our findings demonstrate higher sensitivity of DENV IgG ELISA than IgG-capture ELISA in seroprevalence study and interpretation of DENV IgG-capture ELISA should take sampling time and primary or secondary DENV infection into consideration.

Tracing the relationship among HIV-1 sub-subtype F1 strains: a phylodynamic perspective.

BACKGROUND: The human immunodeficiency virus type 1, F1 sub-subtype (HIV-1 F1) circulates in three continents: Africa, Europe, and South America. In Brazil, this sub-subtype co-circulates with subtypes B and C and several recombinant forms, mainly BF1 variants. OBJECTIVES: This study aimed to reconstruct the dynamic history of HIV-1 F1 in Brazil. METHODS: HIV-1 near full-length genome and pol gene nucleotide sequences available in public databases were assembled in two datasets (POL671 and NFLG53) to cover the largest number of F1 sub-subtype sequences. Phylodynamic and temporal analyses were performed. FINDINGS: Two main strains of the F1 sub-subtype are circulating worldwide. The first (F1.I) was found among Brazilian samples (75%) and the second (F1.II) among Romanian (62%) and other European and African isolates. The F1 subtype epidemic in Brazil originated from a single entry into the country around 1970. This ancestral sample is related to samples isolated in European countries (France, Finland, and Belgium), which are possibly of African origin. Moreover, further migration (1998 CI: 1994-2003) of strains from Brazil to Europe (Spain and the UK) was observed. Interestingly, all different recombinant BF patterns found, even those from outside Brazil, present the same F1 lineage (F1.I) as an ancestor, which could be related to the acquisition of adaptive advantages for the recombinant progenies. MAIN CONCLUSIONS: These findings are important for the understanding of the origin and dynamics of the F1 sub-subtype and a consequent better and greater understanding of the HIV-1 F1 and BF epidemic that still spreads from Brazil to other countries.

Low Quality of Life, Falls, and Pre-Frailty are Associated with Depressive Symptoms in Virologically Suppressed PLWHIV in Salvador, Brazil.

Depression is the leading cause of years lived with disability worldwide and PLWHIV present a higher risk of developing depressive symptoms. We aimed to evaluate depressive symptoms and their predictors in virologically suppressed PLWHIV. We conducted a cross-sectional study with 200 PLWHIV. Depressive symptoms were defined as scoring ≥ 14 points in the Beck Depression Inventory II. Most of the participants (58.5%) were men, with a median age of 54 years (IQR: 46.25-59.00). Depressive symptoms' prevalence was 19.5% and they were associated with being divorced/widowed (aOR: 2.93, CI 95%: 1.17-7.37), recurrent falls (aOR: 4.24, CI 95%: 1.07-16.85), pre-frailty (aOR: 3.55, CI 95%: 1.47-8.57), and lower scores in all HRQoL dimensions. Although virologically suppressed PLWHIV presented lower prevalence of depressive symptoms than reported in previous studies in Brazil and South America, they were associated with falls and frailty, highlighting the need for screening.

RESUMEN: La depresión es la principal causa de años vividos con discapacidad en todo el mundo y las PVVIH presentan un mayor riesgo de desarrollar síntomas depresivos. Nuestro objetivo fue evaluar los síntomas depresivos y sus predictores en PVVIH que tienen supresión viral. Fue realizado un estudio de corte transversal incluyendo 200 PVVIH. La presencia de síntomas depresivos fue definida con una puntuación ≥ 14 puntos en el Inventario de Depresión de Beck II. La mayoría de los participantes (58.5%) fueron hombres, la mediana de edad fue de 54 años (RIQ: 46.25­59.00), y la prevalencia de síntomas depresivos fue de 19.5%. La depresión estuvo asociada con ser divorciado/viudo (ORa: 2.93, IC 95%: 1.17­7.37), caídas recurrentes (ORa: 4.24, IC 95%: 1.07­16.85) y prefragilidad (ORa: 3.55, IC 95%: 1.47­8.57). Los pacientes con síntomas depresivos tuvieron puntuaciones más bajas en todas las dimensiones de la escala de calidad de vida. Aunque encontramos una baja prevalencia de síntomas depresivos en PVVIH con supresión virológica en comparación con estudios previos en Brasil y Sudamérica, los factores asociados resaltan la importancia de la identificación temprana de caídas y fragilidad en esta población.

Chlorhexidine mouthwash reduces the salivary viral load of SARS-CoV-2: A randomized clinical trial.

OBJECTIVES: This study aimed to evaluate the effect of 0.12% chlorhexidine gluconate on the salivary load of SARS-CoV-2. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled trial was performed on 100 participants positive for SARS-CoV-2. In the test group (n = 50), volunteers gargled with a mouthwash containing 15 ml of 0.12% chlorhexidine gluconate for 1 min, while the control group (n = 50) used a placebo. Saliva samples were obtained before (baseline) and 5 and 60 min after using the solutions. Real-time reverse transcription polymerase chain reaction assays (qRT-PCR) were carried out and the cycle threshold (Ct) was computed. The chi-square test and t-test were used for group comparison (p ≤ 0.05). RESULTS: The differences in Ct values between the 5-min evaluation and baseline (test group: 2.19 ± 4.30; control: -0.40 ± 3.87, p = 0.002) and between 60 min and baseline (test group: 2.45 ± 3.88; control: 0.76 ± 4.41, p = 0.05) were significantly greater in the test group, revealing a reduction of viral load. Furthermore, there was a reduction in the load of SARS-CoV-2 in 72% of the volunteers using chlorhexidine versus 30% in the control group (p = 0.001). CONCLUSIONS: Chlorhexidine gluconate (0.12%) was effective in reducing salivary SARS-CoV-2 load for at least 60 min.

Oral health and quality of life of people living with human T-cell leukemia virus-1 in Salvador, Brazil: a cross-sectional study.

OBJECTIVE: To compare the oral health status and oral health-related quality of life (OHRQoL) in symptomatic and asymptomatic patients with human T-cell leukemia virus-1 (HTLV-1). MATERIAL AND METHODS: This cross-sectional study included 204 seropositive patients, classified into two groups, symptomatic and asymptomatic. The first group included patients with neurological symptoms associated with HTLV-1 (n = 69), and the second group, asymptomatic HTLV-1 carriers (n = 135). We evaluated the total unstimulated saliva flow, oral mucosa, the Decayed, Missing, Filled Teeth (DMFT) index, and Periodontal Screening and Recording (PSR). The Oral Health Impact Profile (OHIP14) measured the oral health-related quality of life. General health-related quality of life was measured by the 36-Item Short-Form Health Survey (SF-36). Variables with a value of p < 0.25 in bivariate analysis were selected, together with SF-36 summaries' scores and total OHIP-14, for composing a logistic regression model that had symptomatology as the dependent variable. RESULTS: The OHIP-14 total score was poor in symptomatic and asymptomatic groups, but with no marked difference between them. Symptomatic patients showed significantly lower SF-36 scores (P ≤ 0.05) compared to asymptomatic ones, except for mental component summary (MCS). Family income (1-2.99 minimal wages), reduced salivary flow, flossing, and lower physical component summary (PCS) were associated (P ≤ 0.05) with symptomatology. CONCLUSIONS: Symptomatic individuals living with HTLV-1 showed lower HRQoL and poorer OHRQoL compared to asymptomatic ones. Family income, flossing, reduced salivary flow, and lower PCS were associated with symptomatic HTLV-1 individuals. CLINICAL RELEVANCE: In the present study, symptomatic individuals with HTLV-1 showed higher family income, poorer oral health status, lower salivary flow, poorer OHRQoL, and lower HRQoL compared to asymptomatic ones.

Thermal enhancement of upconversion emission in nanocrystals: a comprehensive summary.

Luminescence thermal stability is a major figure of merit of lanthanide-doped nanoparticles playing an essential role in determining their potential applications in advanced optics. Unfortunately, considering the intensification of multiple electron-vibration interactions as temperature increases, luminescence thermal quenching of lanthanide-doped materials is generally considered to be inevitable. Recently, the emergence of thermally enhanced upconversion luminescence in lanthanide-doped nanoparticles seemed to challenge this stereotype, and the research on this topic rapidly aroused wide attention. While considerable efforts have been made to explore the origin of this phenomenon, the key mechanism of luminescence enhancement is still under debate. Here, to sort out the context of this intriguing finding, the reported results on this exciting topic are reviewed, and the corresponding enhancement mechanisms as proposed by different researchers are summarized. Detailed analyses are provided to evaluate the contribution of the most believed "surface-attached moisture desorption" process on the overall luminescence enhancement of lanthanide-doped nanoparticles at elevated temperatures. The impacts of other surface-related processes and shell passivation on the luminescence behaviour of the lanthanide-doped materials are also elaborated. Lack of standardization in the reported data and the absence of important experimental information, which greatly hinders the cross-checking and reanalysis of the results, is emphasized as well. On the foundation of these discussions, it is realized that the thermal-induced luminescence enhancement is a form of recovery process against the strong luminescence quenching in the system, and the enhancement degree is closely associated with the extent of luminescence loss induced by various quenching effects beforehand.

Inert Shell Effect on the Quantum Yield of Neodymium-Doped Near-Infrared Nanoparticles: The Necessary Shield in an Aqueous Dispersion.

Lanthanide-doped nanoparticles (LnNPs) are versatile near-infrared (NIR) emitting nanoprobes that have led to their growing interest for use in biomedicine-related imaging. Toward the brightest LnNPs, high photoluminescence quantum yield (PLQY) values are attained by implementing core/shell engineering, particularly with an optically inert shell. In this work, a thorough investigation is performed to quantify how an outer inert shell maintains the PLQY of Nd3+-doped LnNPs dispersed in an aqueous environment. Three relevant quantitative findings affecting the PLQY of Nd3+-doped LnNPs are identified: (i) the PLQY of core LnNPs is improved 3-fold upon inert shell coating; (ii) PLQY decreases with increasing Nd3+ doping despite the inert shell; and (iii) solvent quenching has a major influence on the PLQY of the LnNPs, though it is relatively lessened for high Nd3+ doping. Overall, we shed new light on the impact of the LnNP architecture on the NIR emission, as well as on the quenching effects caused by doping concentration and solvent molecules.

Exploring Single-Nanoparticle Dynamics at High Temperature by Optical Tweezers.

The experimental determination of the velocity of a colloidal nanoparticle (vNP) has recently became a hot topic. The thermal dependence of vNP is still left to be explored although it is a valuable source of information allowing, for instance, the discernment between ballistic and diffusive regimes. Optical tweezers (OTs) constitute a tool especially useful for the experimental determination of vNP although they have only been capable of determining it at room temperature. In this work, we demonstrate that it is possible to determine the temperature dependence of the diffusive velocity of a single colloidal nanoparticle by analyzing the temperature dependence of optical forces. The comparison between experimental results and theoretical predictions allowed us to discover the impact that the anomalous temperature dependence of water properties has on the dynamics of colloidal nanoparticles in this temperature range.

Real-Time Intracellular Temperature Imaging Using Lanthanide-Bearing Polymeric Micelles.

Measurement of thermogenesis in individual cells is a remarkable challenge due to the complexity of the biochemical environment (such as pH and ionic strength) and to the rapid and yet not well-understood heat transfer mechanisms throughout the cell. Here, we present a unique system for intracellular temperature mapping in a fluorescence microscope (uncertainty of 0.2 K) using rationally designed luminescent Ln3+-bearing polymeric micellar probes (Ln = Sm, Eu) incubated in breast cancer MDA-MB468 cells. Two-dimensional (2D) thermal images recorded increasing the temperature of the cells culture medium between 296 and 304 K shows inhomogeneous intracellular temperature progressions up to ∼20 degrees and subcellular gradients of ∼5 degrees between the nucleolus and the rest of the cell, illustrating the thermogenic activity of the different organelles and highlighting the potential of this tool to study intracellular processes.

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.

Cardiovascular disease among people living with HIV in Brazil.

OBJECTIVES: There is a paucity of data on cardiovascular disease (CVD) among people living with HIV (PLHIV) in resource-limited countries. We assessed factors associated with CVD and the impact of prevalent CVD on all-cause mortality in PLHIV on antiretroviral therapy in Brazil. METHODS: Competing risk regression to assess factors associated with CVD and all-cause mortality in the HIV-Brazil Cohort Study between 2003 and 2014. RESULTS: Among 5614 patients, the rate of CVD was 3.5 (95% confidence interval [95% CI] 2.9-4.3) per 1000 person-years. CVD was associated with older age (adjusted hazard ratio [aHR] 6.4 for ≥55 years vs. <35 years, 95% CI: 2.5-16.3, P < 0.01), black race (aHR 1.8 vs. white race, 95% CI: 1.0-3.1, P = 0.04), past CVD (aHR 3.0 vs. no past CVD, 95% CI: 1.4-6.2, P < 0.01), hypertension (aHR 1.8 vs. no hypertension, 95% CI: 1.0-3.1, P = 0.04), high-grade dyslipidemia (aHR 9.3 vs. no high-grade dyslipidemia, 95% CI: 6.0-14.6, P < 0.01), ever smoking (aHR 2.4 vs. never, 95% CI: 1.2-5.0, P = 0.02) and low nadir CD4 cell count (aHR 1.8 for 100-250 cells/mm3 vs. >250 cells/mm3 , 95% CI: 1.0-3.2, P = 0.05). The rate of death was 16.6 (95% CI: 15.1-18.3) per 1000 person-years. Death was strongly associated with having had a past CVD event (aHR 1.7 vs. no past CVD event, 95% CI: 1.1-2.7, P = 0.01). CONCLUSIONS: Traditional and HIV-specific factors associated with CVD among PLHIV in Brazil are similar to those identified among PLHIV in high-income countries. PLHIV in Brazil with a history of CVD have a high risk of death. CVD care and treatment remain priorities for PLHIV in Brazil as this population ages and antiretroviral therapy use expands.

OBJECTIFS: Il existe peu de données sur les maladies cardiovasculaires (MCV) chez les personnes vivant avec le VIH (PVVIH) dans les pays à ressources limitées. Nous avons évalué les facteurs associés aux MCV et l'impact des MCV prévalentes sur la mortalité toutes causes confondues des PVVIH sous le traitement antirétroviral au Brésil. MÉTHODES: Régression des risques concurrente pour évaluer les facteurs associés aux MCV et à la mortalité toutes causes confondues dans l'étude de cohorte VIH-Brésil entre 2003 et 2014. RÉSULTATS: Parmi 5.614 patients, le taux de MCV était de 3,5 (intervalle de confiance à 95% [IC95%] 2,9-4,3) pour 1.000 personnes-années. Les MCV étaient associées à un âge plus avancé (rapport de risque ajusté [aHR] 6,4 chez les ≥55 ans versus chez les <35 ans, IC95%: 2,5-16,3 ; p <0,01), race noire (aHR: 1,8 versus race blanche, IC95%: 1,0-3,1 ; p = 0,04), MCV passée (aHR: 3,0 versus pas de MCV passée, IC95%: 1,4-6,2 ; p <0,01), hypertension (aHR: 1,8 versus pas d'hypertension, IC95%: 1,0-3,1 ; p = 0,04), dyslipidémie de grade élevé (aHR 9,3 versus absence de dyslipidémie de grade élevé, IC95%: 6,0-14,6 ; p <0,01), tabagisme (aHR 2,4 versus n'avoir jamais fumé, IC95%: 1,2-5,0 ; p = 0,02) et faible nombre de CD4 au nadir (aHR: 1,8 pour 100-250 cellules/mm3 versus >250 cellules/mm3 , IC95%: 1,0-3,2 ; p = 0,05). Le taux de décès était de 16,6 (IC95%: 15,1-18,3) pour 1.000 personnes-années. Le décès était fortement associé à un événement MCV antérieur (aHR: 1,7 versus aucun événement MCV antérieur, IC95%: 1,1-2,7 ; p = 0,01). CONCLUSIONS: Les facteurs traditionnels et spécifiques au VIH associés aux MCV chez les PVVIH au Brésil sont similaires à ceux identifiés chez les PVVIH dans les pays à revenu élevé. Les PVVIH au Brésil ayant des antécédents de MCV ont un risque élevé de décès. Les soins et le traitement des MCV restent des priorités pour les PVVIH au Brésil à mesure que cette population vieillit et que l'utilisation des thérapies antirétrovirales augmente.

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.

The neurodevelopmental spectrum of congenital Zika infection: a scoping review.

AIM: To describe the standardized neurodevelopmental outcomes after the first year of life in children with congenital Zika syndrome (CZS) and those exposed to Zika virus (ZIKV) during fetal life, but without microcephaly at birth. METHOD: This scoping review included observational studies about the standardized neurodevelopmental outcome in children with CZS or exposed to ZIKV, but without microcephaly, assessed after 12 months of age. The databases searched were MEDLINE/Pubmed, LILACS, Scielo, Scopus, PsycINFO, CINAHL, and Embase. Risk of bias was assessed with the Joanna Briggs Institute Critical Appraisal Checklists. RESULTS: Seventeen papers were included: 12 focused on children with CZS, four on children born without microcephaly, and one described both. Only one of the studies about CZS reported a child with microcephaly and typical development; the remainder described a severe pattern of global developmental delay and cerebral palsy. The prevalence of epilepsy was 74.6%. In the reports about children born without microcephaly, 6.9% to 8.7% had some domain with a score below -2 SD, and three children developed autism spectrum disorder. INTERPRETATION: CZS is associated with severe global developmental delay and cerebral palsy after 1 year of age. In children born without microcephaly, although most have typical development, some may be at risk for impairments.

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.

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.

Combination of Nonstructural Protein 1-Based Enzyme-Linked Immunosorbent Assays Can Detect and Distinguish Various Dengue Virus and Zika Virus Infections.

The recent outbreaks of Zika virus (ZIKV) and associated birth defects in regions of dengue virus (DENV) endemicity emphasize the need for sensitive and specific serodiagnostic tests. We reported previously that enzyme-linked immunosorbent assays (ELISAs) based on the nonstructural protein 1 (NS1) of DENV serotype 1 (DENV1) and ZIKV can distinguish primary DENV1, secondary DENV, and ZIKV infections. Whether ELISAs based on NS1 proteins of other DENV serotypes can discriminate various DENV and ZIKV infections remains unknown. We herein developed DENV2, DENV3, and DENV4 NS1 IgG ELISAs to test convalescent- and postconvalescent-phase samples from reverse transcription-PCR-confirmed cases, including 25 primary DENV1, 24 primary DENV2, 10 primary DENV3, 67 secondary DENV, 36 primary West Nile virus, 38 primary ZIKV, and 35 ZIKV with previous DENV infections as well as 55 flavivirus-naive samples. Each ELISA detected primary DENV infection with a sensitivity of 100% for the same serotype and 23.8% to 100% for different serotypes. IgG ELISA using a mixture of DENV1-4 NS1 proteins detected different primary and secondary DENV infections with a sensitivity of 95.6% and specificity of 89.5%. The ZIKV NS1 IgG ELISA detected ZIKV infection with a sensitivity of 100% and specificity of 82.9%. On the basis of the relative optical density ratio, the combination of DENV1-4 and ZIKV NS1 IgG ELISAs distinguished ZIKV with previous DENV and secondary DENV infections with a sensitivity of 91.7% to 94.1% and specificity of 87.0% to 95.0%. These findings have important applications to serodiagnosis, serosurveillance, and monitoring of both DENV and ZIKV infections in regions of endemicity.

Non-F HBV/HDV-3 coinfection is associated with severe liver disease in Western Brazilian Amazon.

The clinical outcome of hepatitis B virus (HBV) infection may be related to host and viral genetic factors, as well as to the type of infection (monoinfection and coinfection). To analyze the distribution/combination of HBV/hepatitis D virus (HDV) genotypes and the associated clinical characteristics, 409 serum samples from patients with chronic HBV (94 of them coinfected by HDV) followed at the Viral Hepatitis Referral Center of Rio Branco, Brazil were enrolled. HBV DNA and HDV RNA were amplified, respectively, by polymerase chain reaction (PCR) and nested PCR using specific primers in the PreC/C region and the S gene, and by reverse-transcription PCR and seminested PCR using specific primers in the delta antigen region and sequenced. The proportion of women (56.1%) was significantly higher than males in this cohort ( P < 0.01). Women were significantly younger (39.8 years; 8-77 years) than males (44.7 years; 12-79 years; P < 0.01). Sixty-eight (18%) patients were infected with HBV-F genotype and 264 (69.8%) with HBV/non-F genotypes. Coinfection by HDV was detected in 23.9% (94 of 409) of this population and was more frequent in male (54.2%, 51 of 94) than in female patients (44.7%, 42 of 94; P = 0.015). HDV-3 was the most prevalent (88.9%) genotype. Almost 70% of HDV-3 coinfected patients were infected with HBV/non-F genotypes. Severe liver disease was diagnosed in 41 patients, 60.9% (25 of 41) of them coinfected with HDV. HBV/HDV coinfection was associated with male sex, age above 30 years, severe liver disease, and increased alanine aminotransferase levels. HBV/HDV-3 coinfection is associated with severe liver disease, in Rio Branco, Brazil.

Congenital Zika Virus Infection with Normal Neurodevelopmental Outcome, Brazil.

We describe a case of a 20-month-old girl with probable congenital Zika virus infection and normal neurodevelopment, despite microcephaly and abnormal neuroimaging. This case raises questions about early prognostic markers and draws attention to the need for investigation in suspected Zika cases, even if the child's early neurodevelopment is normal.

Use of Urea Wash ELISA to Distinguish Zika and Dengue Virus Infections.

Serologic testing remains crucial for Zika virus diagnosis. We found that urea wash in a Zika virus nonstructural protein 1 IgG ELISA distinguishes secondary dengue virus infection from Zika virus infection with previous dengue (sensitivity 87.5%, specificity 93.8%). This test will aid serodiagnosis, serosurveillance, and monitoring of Zika complications in dengue-endemic regions.