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Propolis is a resinous substance collected by bees (Apis mellifera). It is used for its biological properties. This natural product is available as a safe therapeutic option. Herein, we report the antiviral effects of brown propolis extract from Mexico and green and red propolis extracts from Brazil, as well as their phenolic compounds (quercetin, caffeic acid, and rutin) in preventing infection of MRC-5 cells by HCoV-229E. Normal human fibroblast lung cells (MRC-5) were used to determine the cytotoxicity of the compounds. All samples studied showed antiviral activity. Green and brown propolis extracts, and quercetin exhibited the best EC50 values with values of 19.080, 11.240, and 77.208 µg/mL against HCoV-229E, respectively, and with TC50 of 62.19, 29.192, and 298 µg/mL on MRC-5 cells, respectively. These results are the first in vitro study of the effects of propolis on HCoV-229E and provide the basis for the development of natural formulations against other coronavirus strains. [ABSTRACT FROM AUTHOR]

Background: Several HCV patients in Brazil were lost to follow-up (LTFU) in the last two decades before achievement of sustained virological response (SVR). Strategies to recall those diagnosed but untreated patients have been used elsewhere with different success rates. Aim: To identify and retrieve LTFU patients in order to offer them the treatment with the current highly effective direct acting antiviral agents (DAAs). Methods: Registries ofall HCV patients from three large reference centers in Brazil were retrospectively reviewed to identify those with no registry of SVR. Reasons for non-achievement of SVR were elicited in HCV-RNA + patients. All patients who were not treated or cured were contacted to offer the therapy with DAAs. Results: 10,289 HCV patients (50% males, mean age 52 ± 11 years) were identified. Only 4,293 (41.7%) had been successfully treated previously. From the remaining 5,996 most were LTFU (59%), were not treated for other reasons (14.7%) or were non-responders (26.3%). After revision of the charts 3,559 were considered eligible to be retrieved. The callback success of phone calls was 18%, 13% to cellphone messages (SMS or WhatsApp) and 7% to regular mail. Five-hundred sixty patients had been already treatedor were on treatment and 234 were reported to be dead or transplanted. Finally, 201 had made an appointment and initiated antiviral treatment. Conclusion: Even considering the low callback rate, retrieval of LTFU patients was shown to be an important strategy forhepatitis C micro-elimination in Brazil. [ABSTRACT FROM AUTHOR]

COVID-19 has overwhelmed health services globally. Oral antiviral therapies are licensed worldwide, but indications and efficacy rates vary. We aimed to evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19. We conducted a multicentre, open-label, randomised controlled trial of oral favipiravir in adult patients who were newly admitted to hospital with proven or suspected COVID-19 across five sites in the UK (n=2), Brazil (n=2) and Mexico (n=1). Using a permuted block design, eligible and consenting participants were randomly assigned (1:1) to receive oral favipiravir (1800 mg twice daily for 1 day; 800 mg twice daily for 9 days) plus standard care, or standard care alone. All caregivers and patients were aware of allocation and those analysing data were aware of the treatment groups. The prespecified primary outcome was the time from randomisation to recovery, censored at 28 days, which was assessed using an intention-to-treat approach. Post-hoc analyses were used to assess the efficacy of favipiravir in patients aged younger than 60 years, and in patients aged 60 years and older. The trial was registered with clinicaltrials.gov, NCT04373733. Between May 5, 2020 and May 26, 2021, we assessed 503 patients for eligibility, of whom 499 were randomly assigned to favipiravir and standard care (n=251) or standard care alone (n=248). There was no significant difference between those who received favipiravir and standard care, relative to those who received standard care alone in time to recovery in the overall study population (hazard ratio [HR] 1·06 [95% CI 0·89–1·27]; n=499; p=0·52). Post-hoc analyses showed a faster rate of recovery in patients younger than 60 years who received favipiravir and standard care versus those who had standard care alone (HR 1·35 [1·06–1·72]; n=247; p=0·01). 36 serious adverse events were observed in 27 (11%) of 251 patients administered favipiravir and standard care, and 33 events were observed in 27 (11%) of 248 patients receiving standard care alone, with infectious, respiratory, and cardiovascular events being the most numerous. There was no significant between-group difference in serious adverse events per patient (p=0·87). Favipiravir does not improve clinical outcomes in all patients admitted to hospital with COVID-19, however, patients younger than 60 years might have a beneficial clinical response. The indiscriminate use of favipiravir globally should be cautioned, and further high-quality studies of antiviral agents, and their potential treatment combinations, are warranted in COVID-19. LifeArc and CW+. [ABSTRACT FROM AUTHOR]

Direct-acting antivirals are the gold-standard treatment for chronic HCV infections, but few studies have investigated their use on kidney and liver transplant recipients. We conducted a real-world study to evaluate the rates of sustained virological response with direct-acting antivirals in kidney and liver transplant recipients. Moreover, it also aimed to evaluate direct-acting antivirals (DAAs) interference with immunosuppressant levels and to describe the frequency of adverse events. As part of this retrospective observational cohort, we included adult patients that had undergone a kidney transplant (KT) or liver transplant (LT) at our center, had a chronic HCV infection, and were treated with DAAs from June 2016 to December 2021. A total of 165 patients were included in the analysis, divided in 108 KT and 57 LT recipients. HCV genotype 1 was more frequent in KT (58.4%), and genotype 3 was more prevalent in LT (57.9%) patients. Sustained virological response was achieved in 89.6% of patients. Adverse effects were reported by 36% of patients. There were significant interactions with immunosuppressants requiring dose adjustments. A total of three episodes of rejection were reported in KT recipients. In conclusion, DAA treatment resulted in high rates of SVR and was well tolerated in both kidney and liver transplant patients. Adverse events were frequent but not severe in most patients, with low treatment drop-out rates. Interactions with immunosuppressants need monitoring since dose adjustments may be required. Reporting real-life experiences is important to help build evidence for patient management in non-controlled environments. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) mutations associated with antiviral resistance have become a major problem related to high mortality in kidney transplant patients. The aim of the study was to investigate mutations in the CMV genes UL97 and UL54 associated with antiviral resistance. A retrospective observational cohort study was carried out at Hospital Ophir Loyola (HOL), a reference in Kidney Transplantation. A total of 81 patients who underwent kidney transplantation were followed up between 2016 and 2018 were monitored for CMV viral load by performing qPCR. Sanger sequencing was performed on 66 patients. All CMV-positive kidney transplant recipients were included. Mutations were observed in 15 samples (22.72%) from patients. Most cases involved UL97 mutations. Mutation in UL54 without mutation in UL97 was detected in only 2 cases. Resistance mutations in UL97 were identified, such as M460V, L595S, H520Q, two co-mutations D465R + Del524 and A594P + D413A and a 3 codon deletion (del598-601). The search for mutations in the CMV genes identified mutations that confer resistance to conventional antivirals, such as ganciclovir and cidofovir, used in the treatment of these patients. Confirmation of the association with increased CMV viral load in transplanted patients, due to mutation in resistance genes, requires phenotypic analysis for confirmation purposes. These were the first findings in patients in northern Brazil that we know of. [ABSTRACT FROM AUTHOR]

Mayaro virus is an emerging arbovirus that causes nonspecific febrile illness or arthralgia syndromes similar to the Chikungunya virus, a virus closely related from the Togaviridae family. MAYV outbreaks occur more frequently in the northern and central-western states of Brazil; however, in recent years, virus circulation has been spreading to other regions. Due to the undifferentiated initial clinical symptoms between MAYV and other endemic pathogenic arboviruses with geographic overlapping, identification of patients infected by MAYV might be underreported. Additionally, the lack of specific prophylactic approaches or antiviral drugs limits the pharmacological management of patients to treat symptoms like pain and inflammation, as is the case with most pathogenic alphaviruses. In this context, this review aims to present the state-of-the-art regarding the screening and development of compounds/molecules which may present anti-MAYV activity and infection inhibition. [ABSTRACT FROM AUTHOR]

Background Prolonged QTc intervals and life-threatening arrhythmias (LTA) are potential drug-induced complications previously reported with antimalarials, antivirals, and antibiotics. Our objective was to evaluate the prevalence and predictors of QTc interval prolongation and incidences of LTA during hospitalization for coronavirus disease 2019 (COVID-19) among patients with normal admission QTc. Methods We enrolled 110 consecutive patients in a multicenter international registry. A 12-lead electrocardiograph was performed at admission, after 7, and at 14 days; QTc values were analyzed. Results After 7 days, 15 (14%) patients developed a prolonged QTc (pQTc; mean QTc increase 66 ± 20 msec; +16%; P <.001); these patients were older and had higher basal heart rates, higher rates of paroxysmal atrial fibrillation, and lower platelet counts. The QTc increase was inversely proportional to the baseline QTc level and leukocyte count and directly proportional to the basal heart rate (P <.01). We conducted a multivariate stepwise analysis including age, male gender, paroxysmal atrial fibrillation, basal QTc values, basal heart rate, and dual antiviral therapy; age (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.00–1.13; P <.05), basal heart rate (OR, 1.07; 95% CI, 1.02–1.13; P <.01), and dual antiviral therapy (OR, 12.46; 95% CI, 2.09–74.20; P <.1) were independent predictors of QT prolongation. The incidence rate of LTA during hospitalization was 3.6%. There was 1 patient who experienced cardiac arrest and 3 with nonsustained ventricular tachycardia. LTAs were recorded after a median of 9 days from hospitalization and were associated with 50% of the mortality rate. Conclusions After 7 days of hospitalization, 14% of patients with COVID-19 developed pQTc; age, basal heart rate, and dual antiviral therapy were found to be independent predictors of pQTc. Life-threatening arrhythmias have an incidence rate of 3.6%, and were associated with a poor outcome. [ABSTRACT FROM AUTHOR]

In search of new antiviral compounds against Zika virus we conducted a bioassay-guided fractionation of bisbenzyilisoquinoline alkaloids isolated from Cissampelos sympodialis (Menispermaceae), a medicinal plant species endemic to Brazil. Six subfractions were obtained from a tertiary alkaloidal fraction of the rhizomes (TAFrz) using preparative high-performance liquid chromatography. All the subfractions were tested against Zika virus-infected Vero cells as the cellular model to evaluate cytotoxicity and antiviral effective concentrations. The results showed that three of the six TAFrz subfractions tested were active. The most active ones were the subfraction 6 (that consisted of the alkaloids methylwarifteine and warifteine present as a mixture at a ratio of 8.8:1.2 respectively) and the subfraction 5, that was later identified as warifteine, the major tertiary alkaloid of this species. Warifteine was able to significantly reduce virus titer in Zika virus-infected Vero cells with an IC50 of 2.2 μg/ml and this effect was selective (selectivity index, SI = 68.3). Subfraction 6 had an IC50 = 3.5 μg/ml and was more cytotoxic than pure warifteine, with SI = 6.14. Fraction 5 and fraction 6 were more potent in decreasing the viral titer of Zika virus-infected Vero cells than 6-methylmercaptopurine riboside (IC50 = 24.5 μg/ml and SI = 11.9), a mercaptopurine riboside with ZIKV antiviral activity used as a positive control. Our data demonstrate that alkaloids of the bisbenzylisoquinoline type may be explored as new antiviral agents or as an useful pharmacophore for investigating ZIKV antiviral activity. [ABSTRACT FROM AUTHOR]

Virologic failure may occur because of poor treatment adherence and/or viral drug resistance mutations (DRM). In Brazil, the northern region exhibits the worst epidemiological scenarios for the human immunodeficiency virus (HIV). Thus, this study is aimed at investigating the genetic diversity of HIV-1 and DRM in Manaus. The cross-sectional study included people living with HIV on combined antiretroviral therapy and who had experienced virological failure during 2018-2019. Sequencing of the protease/reverse transcriptase (PR/RT) and C2V3 of the viral envelope gp120 (Env) regions was analyzed to determine subtypes/variants of HIV-1, DRMs, and tropism. Ninety-two individuals were analyzed in the study. Approximately 72% of them were male and 74% self-declared as heterosexual. Phylogenetic inference (PR/RT-Env) showed that most sequences were B subtype, followed by BF1 or B C mosaic genomes and few F1 and C sequences. Among the variants of subtype B at PR/RT, 84.3% were pandemic ( B PAN ), and 15.7% were Caribbean ( B CAR ). The DRMs most frequent were M184I/V (82.9%) for nucleoside reverse transcriptase inhibitors (NRTI), K103N/S (63.4%) for nonnucleoside reverse transcriptase inhibitor (NNRTI), and V82A/L/M (7.3%) for protease inhibitors (PI). DRM analysis depicted high levels of resistance for lamivudine and efavirenz in over 82.9% of individuals; although, low (7.7%) cross-resistance to etravirine was observed. A low level of resistance to protease inhibitors was found and included patients that take atazanavir/ritonavir (16.6%) and lopinavir (11.1%), which confirms that these antiretrovirals can be used—for most individuals. The thymidine analog mutations-2 (TAM-2) resistance pathway was higher in B CAR than in B PAN . Similar results from other Brazilian studies regarding HIV drug resistance were observed; however, we underscore a need for additional studies regarding subtype B CAR variants. Molecular epidemiology studies are an important tool for monitoring the prevalence of HIV drug resistance and can influence the public health policies. [ABSTRACT FROM AUTHOR]

The efficacy of direct-acting antivirals (DAAs) in the treatment of chronic hepatitis C (CHC) in liver transplant recipients is poorly understood, and several factors, including immunosuppression, drug interactions, elevated viraemia, and intolerance to ribavirin (RBV), can reduce cure rates. We conducted a real-life study on liver transplant recipients with CHC treated with a combination of sofosbuvir (SOF) and daclatasvir (DCV) or simeprevir (SIM), with or without RBV, followed-up for 12 to 24 weeks. The treatment effectiveness was assessed by determining the sustained virological response (SVR) rates at 12 or 24 weeks after the treatment cessation. Eighty-four patients were evaluated, with a mean age of 63.4 ± 7.4 years, HCV genotype 1 being the most prevalent (63.1%). Nineteen patients (22.7%) had mild fibrosis (METAVIR < F2) and 41 (48.8%) significant fibrosis (METAVIR = F2). The average time between liver transplantation and the start of treatment was 4 years (2.1-6.6 years). The SOF + DCV regimen was used in 58 patients (69%). RBV in combination with DAAs was used in seven patients (8.3%). SVR was achieved in 82 patients (97.6%), and few relevant adverse events could be attributed to DAA therapy, including a patient who stopped treatment due to a headache. There was a significant reduction in ALT, AST, GGT and FA levels, or the APRI index after 4 weeks of treatment, which remained until 12/24 weeks post-treatment. DAA treatment of CHC in liver-transplanted patients achieved a high SVR rate and resulted in the normalization of serum levels of liver enzymes. [ABSTRACT FROM AUTHOR]

Introduction and objectives: Glecaprevir/pibrentasvir is a highly effective and well tolerated treatment for hepatitis C infection. Brazilian patients were not included in the original development studies for glecaprevir/pibrentasvir. This study aimed to assess safety and efficacy of glecaprevir/pibrentasvir in treatment-naïve Brazilian adults without cirrhosis or with compensated cirrhosis. Patients and methods: EXPEDITION-3 was a Phase 3, open-label, multicenter study in treatment-naïve Brazilian adults with hepatitis C infection genotype 1-6. Patients without cirrhosis (F2 or F3) or with compensated cirrhosis (F4) received 8 or 12 weeks of glecaprevir/pibrentasvir, respectively. The primary efficacy endpoint was the rate of sustained virologic response at post-treatment Week 12. Secondary endpoints were on-treatment virologic failure and relapse rates. Baseline polymorphisms were assessed in NS3 and NS5A. Adverse events and laboratory abnormalities were monitored. Results: 100 patients were enrolled, 75 received 8 weeks of treatment and 25 received 12 weeks; all patients completed treatment. Overall sustained virologic response at post-treatment Week 12 rate was high (98.0%; 98/100; 95% confidence interval: 93.0-99.4) and remained high regardless of baseline viral or host factors, including demographics, hepatitis C virus RNA levels, polymorphisms in NS3 and/or NS5A, genotype, and relevant comorbidities. 55% of patients reported =1 adverse event, the most common being headache (18.0%). Four patients reported serious adverse events; none were considered drug related or led to study drug discontinuation. No hepatic decompensations were observed. Conclusions: Glecaprevir/pibrentasvir was effective and well tolerated in treatment-naïve Brazilian patients with hepatitis C infection without cirrhosis and with compensated cirrhosis. [ABSTRACT FROM AUTHOR]

Background: The efficacy and safety of azithromycin in the treatment of COVID-19 remain uncertain. We assessed whether adding azithromycin to standard of care, which included hydroxychloroquine, would improve clinical outcomes of patients admitted to the hospital with severe COVID-19.Methods: We did an open-label, randomised clinical trial at 57 centres in Brazil. We enrolled patients admitted to hospital with suspected or confirmed COVID-19 and at least one additional severity criteria as follows: use of oxygen supplementation of more than 4 L/min flow; use of high-flow nasal cannula; use of non-invasive mechanical ventilation; or use of invasive mechanical ventilation. Patients were randomly assigned (1:1) to azithromycin (500 mg via oral, nasogastric, or intravenous administration once daily for 10 days) plus standard of care or to standard of care without macrolides. All patients received hydroxychloroquine (400 mg twice daily for 10 days) because that was part of standard of care treatment in Brazil for patients with severe COVID-19. The primary outcome, assessed by an independent adjudication committee masked to treatment allocation, was clinical status at day 15 after randomisation, assessed by a six-point ordinal scale, with levels ranging from 1 to 6 and higher scores indicating a worse condition (with odds ratio [OR] greater than 1·00 favouring the control group). The primary outcome was assessed in all patients in the intention-to-treat (ITT) population who had severe acute respiratory syndrome coronavirus 2 infection confirmed by molecular or serological testing before randomisation (ie, modified ITT [mITT] population). Safety was assessed in all patients according to which treatment they received, regardless of original group assignment. This trial was registered at ClinicalTrials.gov, NCT04321278.Findings: 447 patients were enrolled from March 28 to May 19, 2020. COVID-19 was confirmed in 397 patients who constituted the mITT population, of whom 214 were assigned to the azithromycin group and 183 to the control group. In the mITT population, the primary endpoint was not significantly different between the azithromycin and control groups (OR 1·36 [95% CI 0·94-1·97], p=0·11). Rates of adverse events, including clinically relevant ventricular arrhythmias, resuscitated cardiac arrest, acute kidney failure, and corrected QT interval prolongation, were not significantly different between groups.Interpretation: In patients with severe COVID-19, adding azithromycin to standard of care treatment (which included hydroxychloroquine) did not improve clinical outcomes. Our findings do not support the routine use of azithromycin in combination with hydroxychloroquine in patients with severe COVID-19.Funding: COALITION COVID-19 Brazil and EMS. [ABSTRACT FROM AUTHOR]

Coronavirus (COVID-19) has become a pandemic and has recently posed a major threat to public health worldwide, as to date there are no clinically approved vaccines or antiviral drugs available for these infections in humans. The World Health Organization (WHO) has declared the disease as a public emergency of international interest, and the internet has now proved to be the main channel of health information for the general public. COVID-19 reached an unprecedented magnitude, in which there was a drop in China's Gross Domestic Product (GDP), and consequently a drop in the GDP of countries whose people were infected. Prevention measures are based mainly on social isolation, establishing certain restrictions, and quarantining individuals who come from one country to another. With regard to public health, everyone must work as a team to provide an adequate and proportional response to this new disease, since the number of cases per day is increasing in several countries in the world, including mortality, and thus affects the conditions of individuals' lives. In this sense, in Brazil, the Northeast region is concentrating a significant number of cases, which worries health professionals, since the lethality coefficient has increased. Based on a quantitative research through the data made available and updated daily on the website of the Ministry of Health, an analysis of confirmed cases and deaths was carried out in the period from 01/30/2020 to 03/31/2020 in the Northeast region of Brazil. The survey returned an increasing curve for each case from the first confirmed in March to the last day under analysis, resulting in a total of 875 diagnoses presenting their first deaths as of March 25, 2020. Thus, the states with the highest number of infected people resulted in those with the most deaths, due to COVID-19. [ABSTRACT FROM AUTHOR]

• We describe our prior efforts in open drug discovery for Ebola and Zika virus. • We summarize the current literature for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). • We detail computational repurposing efforts and results for SARS-CoV-2. • To be prepared for future outbreaks we argue we need novel broad-spectrum antivirals. • Limitations of these efforts include funding for experimental validation, and this lags behind the computational work. In the past decade we have seen two major Ebola virus outbreaks in Africa, the Zika virus in Brazil and the Americas and the current pandemic of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is a strong sense of déjà vu because there are still no effective treatments. In the COVID-19 pandemic, despite being a new virus, there are already drugs suggested as active in in vitro assays that are being repurposed in clinical trials. Promising SARS-CoV-2 viral targets and computational approaches are described and discussed. Here, we propose, based on open antiviral drug discovery approaches for previous outbreaks, that there could still be gaps in our approach to drug discovery. [ABSTRACT FROM AUTHOR]

Background: Influenza A H1N1 infections carry a significant mortality risk. This study describes inpatients with suspected and confirmed Influenza A H1N1 infection who were prescribed oseltamivir, the risk factors associated with infection, the association between infection and mortality, and the factors associated with in-hospital mortality in infected patients.Methods: This study was a matched case-control study of hospitalized patients who underwent real-time polymerase chain reaction testing for Influenza A H1N1 and were treated with oseltamivir from 2009 to 2015 in a tertiary care hospital. Cases (patients with positive Influenza A H1N1 testing) were matched 1:1 to controls (patients with negative test results).Results: A total of 1405 inpatients who underwent PCR testing and received treatment with oseltamivir were identified in our study and 157 patients confirmed Influenza A H1N1. Almost one third of patients with Influenza A H1N1 were diagnosed in the pandemic period. There was no difference in mortality between cases and controls. Immunocompromised status, requirement of vasoactive drugs, mechanical ventilation, acute hemodialysis, albumin administration, surgical procedures and thoracic procedures and length of stay were associated with increased risk of death in Influenza A H1N1 infected patients.Conclusions: We found no increased risk of mortality for patients with proven Influenza A H1N1 when compared to similar patients without confirmed Influenza. [ABSTRACT FROM AUTHOR]

Since the emergence of Zika virus (ZIKV) in Brazil in 2015, 48 countries and territories in the Americas have confirmed autochthonous cases of disease caused by the virus. ZIKV-associated neurological manifestations and congenital defects make the development of safe and effective antivirals against ZIKV of utmost importance. Here we evaluated the antiviral activity of 6-methylmercaptopurine riboside (6MMPr), a thiopurine nucleoside analogue derived from the prodrug azathioprine, against the epidemic ZIKV strain circulating in Brazil. In all of the assays, an epithelial (Vero) and a human neuronal (SH-SY5Y) cell line were used to evaluate the cytotoxicity and effective concentrations of 6MMPr against ZIKV. Levels of ZIKV-RNA, viral infectious titre and the percentage of infected cells in the presence or absence of 6MMPr were used to determine antiviral efficacy. 6MMPr decreased ZIKV production by >99% in both cell lines in a dose- and time-dependent manner. Interestingly, 6MMPr was 1.6 times less toxic to SH-SY5Y cells compared with Vero cells, presenting a 50% cytotoxic concentrations (CC 50 ) of 460.3 µM and 291 µM, respectively. The selectivity index of 6MMPr for Vero and SH-SY5Y cells was 11.9 and 22.7, respectively, highlighting the safety profile of the drug to neuronal cells. Taken together, these results identify, for the first time, the thiopurine nucleoside analogue 6MMPr as a promising antiviral candidate against ZIKV that warrants further in vivo evaluation. [ABSTRACT FROM AUTHOR]

Background Direct-acting antivirals (DAA) are currently used for the treatment of chronic hepatitis C (HCV). However, few studies describe the adverse effects (AE) associated with DAA therapy in "real-word" cohorts. Aim To evaluate AE in Brazilian chronic HCV patients after DAA-therapy. Setting A reference center for hepatitis treatment in Rio de Janeiro, Brazil. Methods An observational "real-world" study was conducted with 102 chronic HCV patients undergoing DAA therapy for 12 or 24 weeks. The self-reported AE were correlated with cirrhosis status, genotype, age, current therapeutic schemes and comorbidities. Serious AE were also investigated. Main outcome measure Frequency of AE during DAA therapy. Results Overall, mean ± SD age was 60.9 ± 9.4 years, 67% were females, HCV-genotype 1 was the most prevalent (81%) and 74% were cirrhotic. Moreover, all patients reached sustained virological response. About 90% of patients reported at least one AE associated with current treatment, with a mean of 2.7 symptoms per patient. The most frequently reported AE were fatigue (43%), headache (42%), neuropsychiatric symptoms (30%) and nausea (26%). Furthermore, hemoglobin < 12 mg/dL was the most frequent (38%) laboratory abnormality observed. Neuropsychiatric symptoms were the only AE significantly different in treatment-experienced group when compared to naïve patients (41.7 vs. 12.5, P = 0.002). The higher frequency of AE did not correlate with the presence of previous treatment, cirrhosis, genotype, age, current therapeutic schemes with DAA or comorbidities. Conclusion DAA-based therapeutic regimens demonstrated safety in a Brazilian "real-world" cohort of chronic hepatitis C patients. [ABSTRACT FROM AUTHOR]

Background: Non-structural 5A protein (NS5A) resistance-associated substitutions (RASs) have been identified in patients infected with hepatitis C virus (HCV), even prior to exposure to direct-acting antiviral agents (DAAs). Selection for these variants occurs rapidly during treatment and, in some cases, leads to antiviral treatment failure. DAAs are currently the standard of care for hepatitis C treatment in many parts of the world. Nevertheless, in Brazil, the prevalence of pre-existing NS5A RASs is largely unknown. In this study, we evaluated the frequency of naturally occurring NS5A RASs in Brazilian patients infected with HCV as either a monoinfection or coinfection with human immunodeficiency virus (HIV).Methods: Direct Sanger sequencing of the NS5A region was performed in 257 DAA-naïve patients chronically infected with HCV (156 monoinfected with HCV and 101 coinfected with HIV/HCV).Results: The frequencies of specific RASs in monoinfected patients were 14.6% for HCV GT-1a (M28 V and Q30H/R), 6.0% for GT-1b (L31F/V and Y93H), and 22.6% for GT-3a (A30K and Y93H). For HIV/HCV-coinfected patients, the frequencies of RAS were 3.9% for GT-1a (M28 T and Q30H/R), and 11.1% for GT-1b (Y93H); no RASs were found in GT-3a sequences.Conclusions: Substitutions that may confer resistance to NS5A inhibitors exist at baseline in Brazilian DAA-naïve patients infected with HCV GT-1a, -1b, and -3a. Standardization of RAS definitions is needed to improve resistance analyses and to facilitate comparisons of substitutions reported across studies worldwide. Therapeutic strategies should be optimized to efficiently prevent DAA treatment failure due to selection for RASs, especially in difficult-to-cure patients. [ABSTRACT FROM AUTHOR]

Introduction and aim. There is almost no data regarding the efficacy of direct acting antivirals (DAAs) therapy in Brazil. The aim of this historical cohort study is to describe the sustained virologic response (SVR) rate among real-world compensated chronic hepatitis C patients in three hepatology centers from Southern Brazil. Materials and methods. Patients were included if they had at least 12 weeks follow-up after the end of therapy. Patients that were lost to follow-up or had treatment prematurely interrupted for any reason were considered treatment failure in this intention to treat analysis. Results. 219 patients were analyzed. Mean age was 57.4 ± 10.9 years and 142/219 (64.8%) were male. Genotype 1 was present in 166 patients (75.8%; 1a 29.2%, 1b 46.6%); Genotypes 2, 3 and 4 in 8 (3.7%), 43 (19.6%) and 2 (0.9%), respectively. 96 (43.8%) were cirrhotic. 134 (59.5%) were treatment experienced. DAA therapies were: sofosbuvir (SOF) + ribavirin (RBV) in 10 patients; SOF + simeprevir (SMV) ± RBV in 73; SOF + pegylated interferon (PEG-IFN) + RBV in 6; SOF + daclatasvir (DCV) ± RBV in 51, SOF + ledipasvir (LDV) ± RBV in 61, and paritaprevir/ ritonavir + ombitasvir + dasabuvir (PTVr/OBV/DSV) ± RBV in 18 patients. SVR-12 was achieved in 208/219 (95%). Ten patients had virologic failure: 6 cirrhotic, 7 treatment experienced, and 6 either genotype 3 or 1a. No adverse event was attributed to the DAA therapy. Conclusions. Real world experience with DAA therapy in Southern Brazil showed a high rate of SVR and excellent tolerability. Failure to achieve SVR was mainly observed among patients with at least one negative predictor of response: cirrhosis and/or genotypes 1a or 3. [ABSTRACT FROM AUTHOR]

Anti-Flavivirus antibodies are highly cross-reactive and may facilitate Zika virus (ZIKV) infection through the antibody-dependent enhancement (ADE) mechanism. We demonstrate that dengue-specific antibodies enhance the infection of a primary Brazilian ZIKV isolate in a FcγRII-expressing K562 cell line. In addition, we demonstrate that serum samples from dengue-immune pregnant women enhanced ZIKV infection. These findings highlight the need for epidemiological studies and animal models to further confirm the role of ADE in the development of congenital and neurological complications associated with ZIKV infections. [ABSTRACT FROM AUTHOR]

Dictyotaceae algae have gained recognition as prolific producers of diterpenes, which are molecules with significant biotechnological potential. These diterpenes hold immense promise as potential active drug components, making the algae a compelling area of study. The present review aims to present the latest advancements in understanding the biopotential of Brazilian Dictyota and Canistrocarpus brown algae, shedding light on the remarkable diversity and the biological and pharmacological potential of the secondary metabolites they produce. A total of 78 articles featuring 26 distinct diterpenes are reported in this review, with their antiviral potential being the mosthighlighted biological activity. Despite considerable research on these algae and their diterpenes, significant knowledge gaps persist. Consequently, the present review is poised to serve as a pivotal resource for researchers who are actively engaged in the pursuit of active diterpenes beyond the immediate purview. Furthermore, it holds the potential to catalyze an increase in research endeavors centered around these algal species within the geographical confines of the Brazilian coastline. Also, it assumes a critical role in directing future scientific explorations toward a better comprehension of these compounds and their ecological implications.

Purpose - New hepatitis C medicines such as sofosbuvir underline the need to balance considerations of innovation, clinical evidence, budget impact and equity in health priority-setting. The purpose of this paper is to examine the role of public participation in addressing these considerations. Design/methodology/approach - The paper employs a comparative case study approach. It explores the experience of four countries - Brazil, England, South Korea and the USA - in making coverage decisions about the antiviral sofosbuvir and involving the public and patients in these decision-making processes. Findings - Issues emerging from public participation ac tivities include the role of the universal right to health in Brazil, the balance between innovation and budget impact in England, the effect of unethical medical practices on public perception in South Korea and the legitimacy of priority-setting processes in the USA. Providing policymakers are receptive to these issues, public participation activities may be re-conceptualized as processes that illuminate policy problems relevant to a particular context, thereby promoting an agenda-setting role for the public. Originality/value - The paper offers an empirical analysis of public involvement in the case of sofosbuvir, where the relevant considerations that bear on priority-setting decisions have been particularly stark. The perspectives that emerge suggest that public participation contributes to raising attention to issues that need to be addressed by policymakers. Public participation activities can thus contribute to setting policy agendas, even if that is not their explicit purpose. However, the actualization of this contribution is contingent on the receptiveness of policymakers. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C remains one of the main causes of chronic liver disease worldwide and presents a variable natural history ranging from minimal changes to advanced fibrosis and cirrhosis and its complications, such as development of hepatocellular carcinoma. Approximately, 1.45 million people are estimated to be infected by HCV in Brazil representing a major public health issue. The aim of this paper was to review the epidemiology and management of chronic hepatitis C from a Brazilian perspective. The management of chronic hepatitis C has been challenged by the use of noninvasive methods to stage liver fibrosis as an alternative to liver biopsy and the high cost of new interferon-free antiviral treatments. Moreover, the need of cost-effectiveness analysis in hepatitis C and the recent changes in treatment protocols were discussed. [ABSTRACT FROM AUTHOR]

Interleukin-10 (IL-10) is a cytokine that plays an important role in the regulation of the immune system. Gene polymorphisms of IL-10 have been associated with the different expression levels of this cytokine. In hepatitis C virus infection, IL-10 appears to interfere with the progression of disease, viral persistence and the response to therapy. This study investigated genetic variability in the IL-10 gene promoter between patients infected with hepatitis C virus (HCV) and healthy individuals, associating the frequency of polymorphisms with different aspects of viral infection. This is a case-control study with 260 patients who were infected with HCV and 260 healthy individuals. Genotyping of the polymorphisms was performed using the technique of amplification refractory mutation system PCR (ARMS-PCR) for regions of the IL-10 gene promoter (-1082 G/A, -819 C/T, -592 C/A). The frequencies of alleles and genotypes related to polymorphisms in the IL-10 gene promoter showed a higher frequency of the G allele and genotype GG in the -1082 region between the infected group and the control group ( p = 0.005 and p = 0.001, respectively), whereas the AA genotype was significantly more frequent in the control group. The frequencies of the haplotypes GTA and GCC were higher in the group of infected individuals, whereas the haplotype ATA was more frequent in the healthy group ( p < 0.006). It was also observed that the genotypes GG and AG in the region -1082 were significantly more frequent among patients infected with HCV who were in advanced stages of fibrosis and cirrhosis ( p = 0.042). No association was observed between polymorphisms of IL-10 and sustained virologic response (SVR). [ABSTRACT FROM AUTHOR]

Compounds extracted from plants can provide an alternative approach to new therapies. They present characteristics such as high chemical diversity, lower cost of production and milder or inexistent side effects compared with conventional treatment. The Brazilian flora represents a vast, largely untapped, resource of potential antiviral compounds. In this study, we investigate the antiviral effects of a panel of natural compounds isolated from Brazilian plants species on hepatitis C virus (HCV) genome replication. To do this we used firefly luciferase-based HCV sub-genomic replicons of genotypes 2a (JFH-1), 1b and 3a and the compounds were assessed for their effects on both HCV replication and cellular toxicity. Initial screening of compounds was performed using the maximum non-toxic concentration and 4 compounds that exhibited a useful therapeutic index (favourable ratio of cytotoxicity to antiviral potency) were selected for extra analysis. The compounds APS (EC 50 = 2.3 μM), a natural alkaloid isolated from Maytrenus ilicifolia , and the lignans 3 ∗ 43 (EC 50 = 4.0 μM), 3 ∗ 20 (EC 50 = 8.2 μM) and 5 ∗ 362 (EC 50 = 38.9 μM) from Peperomia blanda dramatically inhibited HCV replication as judged by reductions in luciferase activity and HCV protein expression in both the subgenomic and infectious systems. We further show that these compounds are active against a daclatasvir resistance mutant subgenomic replicon. Consistent with inhibition of genome replication, production of infectious JFH-1 virus was significantly reduced by all 4 compounds. These data are the first description of Brazilian natural compounds possessing anti-HCV activity and further analyses are being performed in order to investigate the mode of action of those compounds. [ABSTRACT FROM AUTHOR]

Obesity is increasing in incidence worldwide, especially in women, which can affect the outcome of pregnancy. During this period, viral infections represent a risk to the mother, the placental unit, and the fetus. The Zika virus (ZIKV) outbreak in Brazil has been the cause of congenital Zika syndrome (CZS), with devastating consequences such as microcephaly in newborns. Herein, we analyzed the impact of maternal overweight/obesity on the antiviral factors' expression in the placental tissue of Zika-infected mothers. We accessed placentas from women with and without obesity from 34 public health units (São Paulo) and from Zika-infected mothers with and without obesity from the Clinical Cohort Study of ZIKV pregnant women (Rio de Janeiro, Brazil). We first verified that obesity, without infection, did not alter the constitutive transcriptional expression of antiviral factors or IFN type I/III expression. Interestingly, obesity, when associated with ZIKV infection, showed a decreased transcriptional expression of RIG-I and IFIH1 (MDA-5 protein precursor gene). At the protein level, we also verified a decreased RIG-I and IRF-3 expression in the decidual placenta from the Zika-infected obese group, regardless of microcephaly. This finding shows, for the first time, that obesity associated with ZIKV infection leads to an impaired type I IFN downstream signaling pathway in the maternal-fetal interface.

Ethnopharmacological Relevance: Anadenanthera colubrina (Vell.) Brenan is an endemic tree to South America and different parts of it are used by the population for the treatment of various diseases, as well as in indigenous rituals. This species has high pharmacological potential but may present toxic potential due to the presence of psychotropic compounds., Aim of the Study: To review published studies with the species A. colubrina regarding ethnobotanical, phytochemical, pharmacological and toxicological aspects, as well as discuss perspectives for new research and protection of this species., Materials and Methods: A literature review was performed by accessing published articles on databases such as: PubMed, Science Direct, Scielo, Scopus, Taylor and Francis online, Springer Link, National Center for Biotechnology Information (NCBI), ACS Publications, Chemspider and Google Scholar. The keywords used were: "Anadenanthera colubrina" or "Mimosa colubrina" or "Piptadenia colubrina" or "Piptadenia macrocarpa" or "Piptadenia grata" or "Anadenanthera macrocarpa" and "medicinal plants" or "pharmacological" or "phytochemicals" or "traditional use" or "toxicological" or "ethnobotanical" or "pre-clinical trial" or "clinical". Articles found by database searches and search engines were screened at four stages: (i) title screening, (ii) locality screening, (iii) abstract screening, and (iv) full text. Other articles found through supplementary searches were screened in the full text whenever available. Each article was assessed by three reviewers at the title and abstract screening stages, except for those found in Portuguese databases that were assessed by the native reviewer., Results: This robust tree has been popularly useful for agroeconomic, medicinal and as a hallucinogen in religious rituals. According to the published studies, the main parts of the plant are the bark and seeds that are mostly used for respiratory conditions and as entheogens, respectively. It is a rich traditional herbal medicine with many pharmacological properties such as anti-inflammatory, antinociceptive, antidiarrheal, wound healing, antimicrobial, antitumoral, antioxidant, antiaddictive, insecticide and allelopathic that were described in in vitro and in vivo assays, and approximately 56 compounds were identified, suggesting a therapeutic potential for this species. Although most relate to medicinal uses, these are preliminaries and do not show the mechanism of action. The phytochemical assays showed the presence of phenolic compounds, flavonoids, triterpenes, steroids and alkaloids. Some of the compounds are anadanthoflavone, which is exclusive to this species, and no pharmacological or toxicological studies have yet demonstrated this compound. Another important compound is bufotenine which was isolated from seeds and is related to hallucinogenic and antiviral activity. The extracts made from leaves, bark, gum, and fruits appear to be safe, according to both in vivo and in vitro toxicology testing, which all shown low toxicity. Due to the presence of bufotenine in the seeds, it can be toxic, however, it was not found in toxicological assays with the seed extracts., Conclusions: Therefore, part of the studies confirms the popular use of A. colubrina, however, more assays with isolated compounds and with the different extracts are necessary to corroborate other uses and the mechanism of action of their pharmacological effects needs to discuss in more detail. Therefore, the present review would be identified the gaps and suggests further studies oriented to validate the popular use. Thus, it must be noted that the use of this species must be controlled in order to minimize the environmental impact, as most of the pharmacological potential was shown with the bark and seeds. Due to its wide use in folk medicine, it is part of the Brazilian medicinal species with priority for conservation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Although chronic hepatitis C has been effectively treated with direct-acting antivirals (DAAs), the use of conventional therapy with peg-interferon (Peg-IFN) or (predominantly) ribavirin (RBV), remains widespread. R70Q/H and L/C91M amino acid substitutions in the hepatitis C virus (HCV) core protein may modulate responses to IFN and/or RBV, and are associated with cirrhosis, hepatocellular carcinoma (HCC), insulin resistance, and liver steatosis. We evaluated the R70Q/H and L/C91M substitutions, clinical and epidemiological profiles, and risk factors of Brazilian patients chronically infected with HCV subgenotypes 1a and 1b (HCV-GT1a and HCV-GT1b) unresponsive to IFN and/or RBV therapy. Sequencing and pyrosequencing analyses and sociodemographic and clinical predictive variables were used to assess the relationship between R70Q/H and L/C91M substitutions. Leukocyte counts, ALT levels, and ALT/AST ratios were significantly reduced in treated individuals, but more of these patients had advanced fibrosis and cirrhosis. L91M was more prevalent (19.7%), occurring only in HCV-GT1b, followed by R70Q/P (11.5%) and R70P (1.4%). R70Q/P exhibited higher mean AST, ALT, and GGT values, whereas L91M showed higher mean GGT values. Pyrosequencing of the L91M position revealed mutant subpopulations in 43.75% of samples.

Objective: to learn about the experience of caregivers/mothers providing care to infants exposed to HIV through vertical transmission. Methods: this qualitative study used Symbolic Interactionism as the theoretical framework. A total of 39 caregivers of children exposed to HIV in follow-up at a specialized service were interviewed. Data were analyzed through inductive content analysis. Results: four categories were identified that report on the lonely experience of handling the child's antiretroviral therapy, mainly due to a lack of information or incomplete information; being attentive to required care, such as the use of prophylaxis for pneumonia, vaccines, and other practices restricted to the mother-child interaction; the desire to omit the HIV out of fear of prejudice and fear of the disease, considering future prospects. Conclusion: the HIV and the threat this infection may affect the child cause apprehension and feelings such as fear, guilt and anxiety in the caregivers. Healthcare workers need to work together with mothers so they are able to cope with demands and distress. Only then will the treatment to avoid vertical transmission be efficient and will mother and child be supported during the process, despite apprehension with the outcome. [ABSTRACT FROM AUTHOR]

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Our aim was to analyze factors associated with non-adherence to antiretroviral (ARV) treatment among children and adolescents. A cross-sectional study was carried out involving non-institutionalized children and adolescents between 2 and 20 years of age, addressing non-adherence to ARV treatment, which was defined as taking ≤89% of the medications on the day of the interview and the three previous days. The investigation into the association between non-compliance and the variables of interest was performed using unconditional logistic regression. The independent factors associated with non-adherence were forgetfulness (OR = 3.22; 95%CI = 1.75–5.92), difficulties coping with treatment (OR = 2.65; 95%CI = 1.03–6.79), and living with grandparents (OR = 2.28; 95%CI = 1.08–4.83), whereas a protective effect was found with participation in multidisciplinary activities (OR = 0.49; 95%CI = 0.25–0.96), i.e., this factor indicates that the exposure to the variable is beneficial, promoting adherence. We concluded that forgetting to take the medications and reporting having difficulty coping with ARV treatment are potentially modifiable factors through educational and programmatic actions. Residing with one's grandparents may strongly impact adherence to ARV treatment, indicating the need for the systematic support of these family members. Participation in multidisciplinary activities should be stimulated at health-care services. [ABSTRACT FROM PUBLISHER]

This study evaluated the influence of fludarabine on the pharmacokinetics of busulfan administered orally to patients receiving a conditioning regimen for hematopoietic allogeneic stem cell transplantation (HSCT). Twenty-six patients treated with oral busulfan (1 mg/kg/6 h for 4 days) were divided into two groups according to the concomitant administration of fludarabine (n = 11; 30 mg/m2 for 5 days) or subsequent administration of cyclophosphamide (n = 15; 60 mg/kg for 2 days). Serial blood samples were collected on Day 4 of busulfan administration. Plasma busulfan concentrations were determined by HPLC-UV and the pharmacokinetic parameters were calculated using the WinNonlin program. Patients concomitantly treated with fludarabine showed reduced apparent clearance of busulfan (110.5 mL/h/kg vs. 157.4 mL/h/kg) and higher AUC0-6 (area under the plasma concentrations vs. time curve) than patients subsequently treated with cyclophosphamide (7.9 µg h/mL vs. 5.7 µg h/mL). No association was observed between busulfan AUC0-6 and clinical evolution of the patients. Although plasma busulfan concentrations were higher in patients receiving concomitant fludarabine, myelosuppression-related toxicity was less frequent than in patients treated with busulfan and cyclophosphamide. The results suggest that patients treated with fludarabine should receive 30% lower busulfan doses during conditioning protocols for HSCT. [ABSTRACT FROM AUTHOR]

Abstract: Cantagalo virus (CTGV) is the etiologic agent of a pustular disease in dairy cows and dairy workers in Brazil with important economical and occupational impacts. Nevertheless, no antiviral therapy is currently available. ST-246 is a potent inhibitor of orthopoxvirus egress from cells and has proved its efficacy in cell culture and in animal models. In this work, we evaluated the effect of ST-246 on CTGV replication. Plaque reduction assays indicated that CTGV is 6–38 times more susceptible to the drug than VACV-WR and cowpox virus, respectively, with an EC50 of 0.0086μM and a selective index of >11,600. The analysis of β-gal activity expressed by recombinant viruses in the presence of ST-246 confirmed these results. In addition, ST-246 had a greater effect on the reduction of CTGV spread in comet tail assays and on the production of extracellular virus relative to VACV-WR. Infection of mice with CTGV by tail scarification generated primary lesions at the site of scarification that appeared less severe than those induced by VACV-WR. Animals infected with CTGV and treated with ST-246 at 100mg/kg for 5days did not develop primary lesions and virus yields were inhibited by nearly 98%. In contrast, primary lesions induced by VACV-WR were not affected by ST-246. The analysis of F13 (p37) protein from CTGV revealed a unique substitution in residue 217 (D217N) not found in other orthopoxviruses. Construction of recombinant VACV-WR containing the D217N polymorphism did not lead to an increase in the susceptibility to ST-246. Therefore, it is still unknown why CTGV is more susceptible to the antiviral effects of ST-246 compared to VACV-WR. Nonetheless, our data demonstrates that ST-246 is a potent inhibitor of CTGV replication that should be further evaluated as a promising anti-CTGV therapy. [Copyright &y& Elsevier]

Abstract: Objectives: Hepatitis C therapy in Brazil is expensive due to the cost of antiviral drugs and demands on medical resources. The objective of this study was to estimate the direct costs per patient of chronic hepatitis C therapy in a Brazilian setting. Method: A microcosting study from a public health system perspective. The costs included were those of antiviral drugs, secondary medicines, diagnostic tests, visits to physicians and other professionals, hospitalization, nurse, and pharmaceutical care. All costs were priced in 2010. The values were converted to US $ (2010). Results: The total direct cost of hepatitis C treatment per patient with interferon alpha (IFN) plus ribavirin (RBV) was US $982.25, with peginterferon alpha (PEG) 2a 180 μg plus RBV was US $10,658.08, and with PEG 2b 120 μg plus RBV was US $12,597.63, taking into account entire treatment according to Brazilian guidelines and assuming that all patients completed full treatment. The antiviral drugs are the most expensive element of the cost of treatment, totaling more than 40% of the medical costs of IFN plus RBV therapy and more than 88% of PEG plus RBV therapy. Calculating an average of 10,000 treatments per year, the total direct cost is US $90,346,772.39. According to the Ministry of Health, 90% of the annual total cost of hepatitis C treatment is accounted for by antiviral drugs. Conclusions: In Brazil, antiviral drugs are the most expensive component of hepatitis C treatment. The cost of follow-up and support to patients is minimal compared with the cost of antiviral drugs. [Copyright &y& Elsevier]

Context: Medicinal plants are well known for their use in traditional folk medicine as treatments for many diseases including infectious diseases. Objective: Six Brazilian medicinal plant species were subjected to an antiviral screening bioassay to investigate and evaluate their biological activities against five viruses: bovine herpesvirus type 5 (BHV-5), avian metapneumovirus (aMPV), murine hepatitis virus type 3, porcine parvovirus and bovine respiratory syncytial virus. Materials and methods: The antiviral activity was determined by a titration technique that depends on the ability of plant extract dilutions (25 or 2.5 µg/mL) to inhibit the viral induced cytopathic effect and the extracts' inhibition percentage (IP). Results: Two medicinal plant species showed potential antiviral activity. The Aniba rosaeodora Ducke (Lauraceae) extract had the best results, with 90% inhibition of viral growth at 2.5 µg/mL when the extract was added during the replication period of the aMPV infection cycle. The Maytenus ilicifolia (Schrad.) Planch. (Celastraceae) extracts at a concentration of 2.5 µg/mL exhibited antiviral activity during the attachment phase of BHV-5 (IP = 100%). Discussion and conclusion: The biomonitored fractionation of the active extracts from M. ilicifolia and A. rosaeodora could be a potential tool for identifying their active compounds and determining the exact mechanism of action. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Brazilian medicinal plants traditionally used for the treatment of diarrhoea were investigated for their in vitro antiviral activity against the simian rotavirus SA11. Materials and methods: The ethanolic crude extracts of plants collected in the cerrado of Minas Gerais, Brazil were submitted to phytochemical screening. The cytotoxicity of the extracts was inferred by cellular morphologic alterations. Antiviral activity was assessed by the ability of the extracts to inhibit the cytopathic effect (CPE) of rotavirus on the treated cells. RT-PCR was performed to confirm and/or confront antiviral assay data. Results: The maximum non-toxic concentration ranged from 50 to 500μg/mL. All extracts were toxic at a concentration of 5000μg/mL but no extract showed cytotoxicity at 50μg/mL. The species Byrsonima verbascifolia, Myracrodruon urundeuva, Eugenia dysenterica and Hymenaea courbaril exhibited the strongest in vitro activity against rotavirus. Their extracts prevented the formation of CPE, and RT-PCR analysis detected no amplification of genetic material from rotavirus. Tannins, flavonoids, saponins, coumarins and terpenes were the major classes of natural products found in the leaf extracts that showed antiviral activity. Conclusion: Among the species studied, Byrsonima verbascifolia, Eugenia dysenterica, Hymenaea courbaril and Myracrodruon urundeuva showed potential activity against rotavirus and are worthy of further study. The present study corroborates ethnopharmacological data as a valuable source in the selection of plants with antiviral activity and to some extent validates their traditional uses. [Copyright &y& Elsevier]

Context: The leaves of Spondias tuberosa Arr. Cam. (Anacardiaceae) and Spondias mombin L. have been traditionally used for medicinal purposes. Some studies reveal their antibacterial, antimicrobial, and antiviral properties. Objective: Determine the chemical composition, antioxidant, and antimicrobial activities of Spondias species to justify its ethnopharmacological use. Materials and methods: Spondias species extracts were prepared with methanol:water 80:20 and analyzed by silica gel column chromatography and reversed phase liquid chromatography (HPLC). The antioxidant activity was evaluated by scavenging the radicals 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS•+) and measuring antimicrobial activity (agar well diffusion method, minimum inhibitory concentration and minimum bactericidal concentrations). Results: The HPLC analysis of Spondias extracts demonstrated the occurrence of high yield of flavonoids. Found in S. mombin were quercetin (2.36 ± 0.01 mg/g) and ellagic acid (41.56 ± 0.01 mg/g) and in S. tuberosa species rutin (53.38 ± 1.71 mg/g), quercetin (24.46 ± 0.87 mg/g), and ellagic acid (169.76 ± 0.17 mg/g). The antibacterial activity of the extracts against the various bacteria strains varied from 8.8 to 20.1 mm. MIC values from 62.5 to 125 µg/mL were satisfactory when compared with other plant products. Medium DPPH scavenging activity IC50 for Spondias extracts varied from 0.042 to 0.558 mg/mL and for ABTS from 0.089 to 0.465 mg/mL. DPPH scavenging activity for constituent ellagic acid IC50 = 0.042 mg/mL and for quercetin IC50 = 0.081 mg/mL. Discussion and conclusion: The chemical study of Spondias leaf extracts showed the occurrence of quercetin, rutin and ellagic acid, substances with relevant antioxidant and antimicrobial activities. [ABSTRACT FROM AUTHOR]

Although available for over a decade, use of nonoccupational postexposure prophylaxis (nPEP) remains controversial in the United States. There are concerns over sexual assault survivors' adherence, or lack thereof, leading to increased costs without an appreciable decrease in human immunodeficiency virus (HIV) transmission. This review examines and synthesizes the available literature from the past 10 years to determine the true rates of provision and adherence to nPEP regimens in sexual assault survivors in low HIV prevalence, industrialized nations. Findings suggest that further prospective research is necessary to better understand the process of post-assault nPEP evaluation and subsequent follow-up and adherence. [ABSTRACT FROM AUTHOR]

Aims: To investigate the in vitro antiviral activity of Distictella elongata (Vahl) Urb. ethanol extracts from leaves (LEE), fruits (FEE), stems and their main components. Methods and Results: The antiviral activity was evaluated against human herpesvirus type 1 (HSV-1), murine encephalomyocarditis virus (EMCV), vaccinia virus Western Reserve (VACV-WR) and dengue virus 2 (DENV-2) by the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. LEE presented anti-HSV-1 [EC50 142·8 ± 5·3 μg ml−1; selectivity index (SI) 2·0] and anti-DENV-2 activity (EC50 9·8 ± 1·3 μg ml−1; SI 1·5). The pectolinarin ( 1) isolated from LEE was less active against HSV-1 and DENV-2. A mixture of the triterpenoids ursolic, pomolic and oleanolic acids was also obtained. Ursolic and oleanolic acids have shown antiviral activity against HSV-1. A mixture of pectolinarin ( 1) and acacetin-7- O-rutinoside ( 2) was isolated from FEE and has presented anti-DENV-2 activity (EC50 11·1 ± 1·6 μg ml−1; SI > 45). Besides the antiviral activity, D. elongata has disclosed antioxidant effect. Conclusions: These data shows that D. elongata has antiviral activity mainly against HSV-1 and DENV-2, besides antioxidant activity. These effects might be principally attributed to flavonoids isolated. Significance and Impact of the Study: Distictella elongata might be considered a promising source of anti-dengue fever phytochemicals. [ABSTRACT FROM AUTHOR]

The pigeon feces are vehicle of diseases both for humans and other animal species. In these birds, the most important viral diseases of the digestive tract are transmitted by the paramyxovirus, adenovirus and coronavirus. Avian paramyxoviruses have been isolated from a variety of species of free living and domestic birds worldwide, with several symptoms and clinical signs and economic losses. Paramyxoviruses belong to the Paramyxoviridae family and Avulovirus genus that includes nine serotypes (APMV 1 to 9). Avian adenoviruses belong to the Adenoviridae family and Aviadenovirus genus. In pigeons, cause classical adenovirosis and necrotizing hepatitis. The respiratory and enteric tracts are common targets of coronavirus. They belong to the Coronaviridae family and to 3a and 3c groups. In this study, we described the presence of viral agents in free-living pigeon feces (Columba livia) from the city ofS~o Paulo, Brazil. The feces were processed by negative staining technique (rapid preparation) for transmission electron microscopy. In this technique paramyxoviruses particles, pleomorphic, roughly spherical or filamentous, measuring 100 to 500 nm of diameter containing an envelope covered by spikes, with characteristic helical herring-bone-like nucleocapsid, measuring 15 to 20 nm in diameter, were visualized in 45 (79%) out of 57 feces samples. In 2 (3.5%) samples, paramyxovirus and adenovirus particles were simultaneously visualized. Adenovirus particles were isometric, spherical, characterized as "complete "or" empty ", measuring between 70 and 90 nm in diameter. Paramyxovirus and coronavirus particles were detected in 3 (5.2%) samples. Coronaviruses were pleomorphic with a diameter of 75-160 nm containing a solar corona-shaped envelope, with projections of approximately 20 nm of diameter. Seven (12.3%) samples were negative for viral particles. [ABSTRACT FROM AUTHOR]

We present a systematic review of historical, political, and epidemiologic aspects of AIDS in Brazilian children. Over 25 years, Brazil has developed different strategies to control AIDS in children. Three revisions of criteria for defining AIDS cases in children and nine national guidelines on antiretroviral therapy administration for management of HIV infection were published. These guidelines represent important progress, including aspects of HIV/AIDS surveillance, antiretroviral treatment, opportunistic conditions, prophylaxis, and laboratory testing. Brazil has significantly expanded access to free therapy with different classes of antiretroviral drugs. Initially focusing on treatment for HIV and opportunistic conditions, the scope of treatment guidelines gradually expanded to comprehensive health care for children and adolescents. From 1996 to 2008, the number of AIDS cases and deaths in children has been reduced by 67% and 65%, respectively, as a result of different strategies to prevent mother-to-child transmission of HIV and highly active antiretroviral therapy administration to infected children. Improved morbidity, mortality, and survival of Brazilian children with AIDS demonstrate clear benefits of adopting a policy of free and universal access to antiretroviral drugs associated with comprehensive care. However, important issues remain to be resolved, mainly concerning social, operational, and regional inequalities in coverage and quality of care, and epidemiological surveillance in different regions of the country. This broad review shows that the overall situation of pediatric AIDS in Brazil represents an incomplete process of epidemiologic and demographic transition, with the coexistence of old and new clinical and epidemiologic challenges. [ABSTRACT FROM AUTHOR]

The article discusses a study which aimed to determine, in a cohort of HIV infected patients in Brazil, what factors were independently associated with paradoxical immunologic response (PIR) to Highly Active Antiretroviral Therapy (HAART). The study concluded that PIR seems to be related to a delay in the management of immunodeficient patients, as shown by its negative association with nadir CD4-count.

Aims: To evaluate the antiviral activity of Bignoniaceae species occurring in the state of Minas Gerais, Brazil. Methods and Results: Ethanol extracts of different anatomical parts of bignoniaceous plant species have been evaluated in vitro against human herpesvirus type 1 (HSV-1), vaccinia virus (VACV) and murine encephalomyocarditis virus (EMCV) by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. A total of 34 extracts from 18 plant species selected according to ethnopharmacological and taxonomic criteria were screened. Fifteen of the 34 extracts (44·1%) have disclosed antiviral activity against one or more of the viruses assayed with EC50 values in the range of 23·2 ± 2·5-422·7 ± 10·9 μg ml−1. Conclusions: Twelve of the 34 extracts (35·3%) might be considered promising sources of antiviral natural products, as they have shown EC50 ≤ 100 μg ml−1. The present screening discloses the high potential of the Bignoniaceae family as source of antiviral agents. Significance and Impact of the Study: Active extracts were identified and deserve bioguided studies for the isolation of antiviral compounds and studies on mechanism of action. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the effects of various treatment modalities employed for patients with sudden sensorineural hearing loss (SHL). We retrospectively evaluated the records of patients treated in the sudden hearing loss section of the Otolaryngology Department at Clinic Hospital, School of Medicine, University of São Paulo, Brazil, between 1996 and 2006. Our study included patients with SHL of sudden onset (occurring over a 72-hour period) at equal to or greater than 30 dB at three consecutive frequencies. We divided patients into five groups by profile and treated them with dextran, dexamethasone, acyclovir, nicotinic acid, and papaverine hydrochloride (with or without vitamin A). We performed audiometry at baseline and on days 30, 90, 120, and 180 of treatment. We determined outcome as the difference between day-0 and day-180 pure-tone averages (PTAs). Among the 139 patients evaluated, baseline PTA was similar in all groups. We observed significant improvements in PTAs after 180 days of treatment and noted a significant linear correlation between time from SHL onset to initial visit and recovery. However, no significant difference was evident among the treatment groups. In the treatment of SHL, dextran provided no more benefit than did dexamethasone or acyclovir. Earlier initiation of treatment improves the prognosis for patients with SHL. [ABSTRACT FROM AUTHOR]

The article explores the accessibility of pharmaceutical vaccines and drugs in Brazil. It notes that Brazil has the largest public industrial capacity for fabricating vaccines in Latin America, however it faces critical and chronic problem on technological dependence and pharmaceutical patents rights. It states that it has been able to introduce innovative public policy strategies about the accessibility of essential drugs and vaccines at the national market and the allocation of limited resources to assure supplies of vaccines and antiviral drugs. Furthermore, it mentions that its production capacity for vaccines and pharmaceutical drugs was largely improved and expanded making most favorable outcomes observed among the developing and less developed countries.

Objective: The potential adverse effects of antiretroviral drugs during pregnancy are discrepant and few studies, mostly from Europe, have provided information about pregnancy outcomes of those already on treatment at conception. The aim of this study was to investigate the impact of antiretrovirals (ARVs) on pregnancy outcome according to the timing of treatment initiation in a cohort of pregnant women from Brazil infected with HIV.Methods: A prospective cohort of 696 pregnant women followed up in one single centre between 1996 and 2006 was studied. Patients who had ARV treatment before pregnancy were compared with those treated after the first trimester. The outcomes evaluated were preterm delivery (PTD) (<37 weeks), severe PTD (<34 weeks), low birth weight (LBW) (<2500 g) and very LBW (<1500 g).Results: Patients who were using ARVs pre-conception had higher rates of LBW (33.3% vs 16.5%; p<0.001) and a similar trend for PTD (26.3% vs 17.7%; p = 0.09). Stratification by type of therapy (dual vs highly active antiretroviral therapy (HAART)) according to timing of initiation of ARVs showed that patients who use HAART pre-conception have a higher rate of PTD (20.2% vs 10.2%; p = 0.03) and LBW (24.2% vs 10.2%; p = 0.002). After adjusting for several factors, HAART used pre-conception was associated with an increased risk for PTD (AOR 5.0; 95% CI 1.5 to 17.0; p = 0.009) and LBW (OR 3.6; 95% CI 1.7 to 7.7; p = 0.001).Conclusions: We identified an increased risk for LBW and PTD in patients who had HAART prior to pregnancy. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the incidence and factors associated with the severity of liver fibrosis in 234 coinfected patients in Brazil. Patients were cared for in our clinic, from 1996 to 2004. Eligible patients were defined as patients with documented HIV and hepatitis C virus (HCV) infections and had previously undergone a liver biopsy. Patients with persistently normal alanine aminotransferase (ALT) were also included. The variables selected for study were age, gender, risk category, history of high alcohol consumption, CD4+ T cell count, antiretroviral therapy usage, HCV genotype and duration of HCV infection. Stage of fibrosis was scored as follows: F0, no fibrosis; F1, portal fibrosis with no septa; F2, portal fibrosis with few septa; F3, bridging fibrosis with many septa; and F4, cirrhosis. The liver fibrosis stage was F3 in 39 (16.6%) and F4 in 20(8.5%) patients. Among patients with normal ALT, the liver fibrosis stage was F3–F4 in three patients (5.6%). Predictors of severe liver fibrosis (F3–F4) by multivariate analysis were age (older patients) and genotype 3 (genotype 1 = odds ratio [OR], 0.28; 95% confidence interval [CI], 0.12 0.65). In summary, in the present study severe liver fibrosis was found in 25% of our patients and was associated with an age of more than 38 years at the time of liver biopsy as well as, HCV genotype 3. No differences were found with respect to CD4+ T cell counts although patients with a CD4+ T cell count greater than 50 were excluded. [ABSTRACT FROM AUTHOR]

Background This study sought to assess the diet quality of individuals living with HIV/AIDS who were receiving antiretroviral therapy in São Paulo, Brazil. Methods This cross-sectional study involved 56 HIV-infected adults. Demographic and anthropometric data were collected, and diet quality was measured using the Healthy Eating Index (HEI), modified for Brazilians, which included ten components: adequacy of intake of six different food groups, total fat, cholesterol, dietary fibre and dietary variety. Results Among the individuals assessed, 64.3% of the participants had a diet needing improvement, while 8.7% had a poor diet. The overall HEI score was 68.3 points (SD = 14.9). Mean scores were low for fruits, vegetables, dairy products and dietary fibre; and high for meats and eggs, total fat and cholesterol. The overall HEI score was higher among individuals who were not overweight ( P = 0.003), who were also more likely to achieve dietary goals for dairy products ( P = 0.039) and grains ( P = 0.005). Conclusion Most of these adults living with HIV/AIDS had diets that required improvement, and being overweight was associated with poorer diet quality. Nutritional interventions aimed at maintaining healthy body weight and diet should be taken into account in caring for HIV-infected people. [ABSTRACT FROM AUTHOR]

This study aimed to compare the outcome of an elderly group of AIDS patients with that of a younger group and their features at the time of the diagnosis of AIDS. We evaluated 58 patients aged .60 years and 114 aged 20—39 years, followed for 35.3 months. There was an obvious delay in diagnosing the elderly as they had more AIDS-defining diseases at diagnosis and their most frequent opportunistic infection was pulmonary tuberculosis. Mortality at the time of the diagnosis of AIDS was four times higher in the elderly (24.1% versus 6.1%, P, 0.001). However, when comparing only those submitted to highly active antiretroviral therapy, there was a similar frequency of favourable outcomes; 76.9% in the elderly against 83.1% in the young (P = 0.455). Mean CD4 lymphocyte was 438 cells/mm3 at the end of follow up in the young when compared with 442 cells/mm3 in the elderly (P = 0.945). The types of antiretroviral schema and the number of antivirals per patient were similar in both groups. [ABSTRACT FROM AUTHOR]