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Antônio Alcirley da Silva Balieiro

Bio: Antônio Alcirley da Silva Balieiro is an academic researcher from Oswaldo Cruz Foundation. The author has contributed to research in topics: Malaria & Plasmodium vivax. The author has an hindex of 9, co-authored 18 publications receiving 1091 citations.

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Journal ArticleDOI
24 Apr 2020
TL;DR: The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir.
Abstract: Importance There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high concentration of the drug. Objective To evaluate the safety and efficacy of 2 CQ dosages in patients with severe COVID-19. Design, Setting, and Participants This parallel, double-masked, randomized, phase IIb clinical trial with 81 adult patients who were hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted from March 23 to April 5, 2020, at a tertiary care facility in Manaus, Brazilian Amazon. Interventions Patients were allocated to receive high-dosage CQ (ie, 600 mg CQ twice daily for 10 days) or low-dosage CQ (ie, 450 mg twice daily on day 1 and once daily for 4 days). Main Outcomes and Measures Primary outcome was reduction in lethality by at least 50% in the high-dosage group compared with the low-dosage group. Data presented here refer primarily to safety and lethality outcomes during treatment on day 13. Secondary end points included participant clinical status, laboratory examinations, and electrocardiogram results. Outcomes will be presented to day 28. Viral respiratory secretion RNA detection was performed on days 0 and 4. Results Out of a predefined sample size of 440 patients, 81 were enrolled (41 [50.6%] to high-dosage group and 40 [49.4%] to low-dosage group). Enrolled patients had a mean (SD) age of 51.1 (13.9) years, and most (60 [75.3%]) were men. Older age (mean [SD] age, 54.7 [13.7] years vs 47.4 [13.3] years) and more heart disease (5 of 28 [17.9%] vs 0) were seen in the high-dose group. Viral RNA was detected in 31 of 40 (77.5%) and 31 of 41 (75.6%) patients in the low-dosage and high-dosage groups, respectively. Lethality until day 13 was 39.0% in the high-dosage group (16 of 41) and 15.0% in the low-dosage group (6 of 40). The high-dosage group presented more instance of QTc interval greater than 500 milliseconds (7 of 37 [18.9%]) compared with the low-dosage group (4 of 36 [11.1%]). Respiratory secretion at day 4 was negative in only 6 of 27 patients (22.2%). Conclusions and Relevance The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir. These findings cannot be extrapolated to patients with nonsevere COVID-19. Trial Registration ClinicalTrials.gov Identifier:NCT04323527

852 citations

Posted ContentDOI
11 Apr 2020-medRxiv
TL;DR: Preliminary findings suggest that the higher CQ dosage (10-day regimen) should not be recommended for COVID-19 treatment because of its potential safety hazards.
Abstract: This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

165 citations

Journal ArticleDOI
TL;DR: The incidence of VL is increasing in Brazil, and the State of Tocantins had the highest rate, which was responsible for VL increasing in the North macroregion, though the incidence rate in this region declined between the two study periods.
Abstract: INTRODUCTION Visceral leishmaniasis (VL) is a neglected disease, with territorial expansion and regional differences in Brazil that require explanation. This study aimed to describe changes in the epidemiology of VL in Brazil from 2001 to 2014. METHODS The incidence rates, sociodemographic and clinical data, and case evolution were subgrouped from 2001 to 2006 and from 2007 to 2014 and presented descriptively. Spatial distribution of disease incidence rates and changes in the spatial and temporal pattern were examined. RESULTS: In total, 47,859 VL cases were reported in Brazil between 2001 and 2014, with predominance in the Northeast macroregion (55%), though the incidence rate in this region declined between the two study periods. The State of Tocantins had the highest crude rate (26.2/100,000 inhabitants), which was responsible for VL increasing in the North macroregion. VL predominated in the urban zone (70%), in children under 4 years (34%); however, an increase in the incidence of VL in adults older than 40 years was identified, with 12.3% and 31% in the first and second period, respectively. The mapping of crude rates and autochthonous canine cases showed territorial expansion. The temporal distribution of VL was consistent in Brazil in general, with no pattern observed, but regional differences were found. CONCLUSIONS: The incidence of VL is increasing in Brazil. In addition to the State of Tocantins, which had the highest rate, new outbreaks of VL have occurred in the South macroregion of Brazil with small decreases identified in the incidence rate in the Northeast.

57 citations

Journal ArticleDOI
TL;DR: Ass associations among symptoms of shigellosis and virulence genes of clinical isolates of Shigella spp.
Abstract: Shigellosis is a global human health problem and the incidence is highest among children. In the present work, main Shigella virulence genes was examined by PCR and compared to symptoms of pediatric shigellosis. Thirty Shigella isolates were identified from an etiologic study at which 1,339 children ranging 0-10 years old were enrolled. S. flexneri was the most frequent species reaching 60.0% of isolates, 22.2% were S. sonnei, and 6.6% were both S. dysenteriae and S. boydii. All Shigella infected children had diarrhea, but not all were accompanied by others symptoms of bacillary dysentery. Among major virulence genes, the PCR typing revealed ipaBCD was present in all isolates, followed by IpaH7.8, set-1A, set-1B, sen/ospD3, virF, and invE. The pathogenic potential of the ShET-1B subunit was observed in relation to dehydration (P < 0.001) and ShET-2 related to the intestinal injury (P = 0.033) evidenced by the presence of bloody diarrhea. Our results show associations among symptoms of shigellosis and virulence genes of clinical isolates of Shigella spp.

46 citations

Journal ArticleDOI
TL;DR: Results show that a diverse range of MDRPA are being discharged in an urban stream from a HWWTP in Manaus and that P. aeruginosa strains with ampicillin and amikacin can persist well within it.
Abstract: Multi-drug resistant forms of Pseudomonas aeruginosa (MDRPA) are a major source of nosocomial infections and when discharged into streams and rivers from hospital wastewater treatment plants (HWWTP) they are known to be able to persist for extended periods. In the city of Manaus (Western Brazilian Amazon), the effluent of three HWWTPs feed into the urban Mindu stream which crosses the city from its rainforest source before draining into the Rio Negro. The stream is routinely used by Manaus residents for bathing and cleaning (of clothes as well as domestic utensils) and, during periods of flooding, can contaminate wells used for drinking water. 16S rRNA metagenomic sequence analysis of 293 cloned PCR fragments, detected an abundance of Pseudomonas aeruginosa (P. aeruginosa) at the stream’s Rio Negro drainage site, but failed to detect it at the stream’s source. An array of antimicrobial resistance profiles and resistance to all 14 tested antimicrobials was detected among P. aeruginosa cultures prepared from wastewater samples taken from water entering and being discharged from a Manaus HWWTP. Just one P. aeruginosa antimicrobial resistance profile, however, was detected from cultures made from Mindu stream isolates. Comparisons made between P. aeruginosa isolates’ genomic DNA restriction enzyme digest fingerprints, failed to determine if any of the P. aeruginosa found in the Mindu stream were of HWWTP origin, but suggested that Mindu stream P. aeruginosa are from diverse origins. Culturing experiments also showed that P. aeruginosa biofilm formation and the extent of biofilm formation produced were both significantly higher in multi drug resistant forms of P. aeruginosa. Our results show that a diverse range of MDRPA are being discharged in an urban stream from a HWWTP in Manaus and that P. aeruginosa strains with ampicillin and amikacin can persist well within it.

35 citations


Cited by
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Journal ArticleDOI
TL;DR: The data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection.
Abstract: Background Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. Methods We conducte...

5,532 citations

01 Jan 2020
TL;DR: Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

4,408 citations

Journal ArticleDOI
TL;DR: In this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death.
Abstract: Background Hydroxychloroquine has been widely administered to patients with Covid-19 without robust evidence supporting its use. Methods We examined the association between hydroxychloroqu...

1,357 citations

Journal ArticleDOI
Nicolas Vabret1, Graham J. Britton1, Conor Gruber1, Samarth Hegde1, Joel Kim1, Maria Kuksin1, Rachel Levantovsky1, Louise Malle1, Alvaro Moreira1, Matthew D. Park1, Luisanna Pia1, Emma Risson1, Miriam Saffern1, Bérengère Salomé1, Myvizhi Esai Selvan1, Matthew P. Spindler1, Jessica Tan1, Verena van der Heide1, Jill Gregory1, Konstantina Alexandropoulos1, Nina Bhardwaj1, Brian D. Brown1, Benjamin Greenbaum1, Zeynep H. Gümüş1, Dirk Homann1, Amir Horowitz1, Alice O. Kamphorst1, Maria A. Curotto de Lafaille1, Saurabh Mehandru1, Miriam Merad1, Robert M. Samstein1, Manasi Agrawal, Mark Aleynick, Meriem Belabed, Matthew Brown1, Maria Casanova-Acebes, Jovani Catalan, Monica Centa, Andrew Charap, Andrew K Chan, Steven T. Chen, Jonathan Chung, Cansu Cimen Bozkus, Evan Cody, Francesca Cossarini, Erica Dalla, Nicolas F. Fernandez, John A. Grout, Dan Fu Ruan, Pauline Hamon, Etienne Humblin, Divya Jha, Julia Kodysh, Andrew Leader, Matthew Lin, Katherine E. Lindblad, Daniel Lozano-Ojalvo, Gabrielle Lubitz, Assaf Magen, Zafar Mahmood2, Gustavo Martinez-Delgado, Jaime Mateus-Tique, Elliot Meritt, Chang Moon1, Justine Noel, Timothy O'Donnell, Miyo Ota, Tamar Plitt, Venu Pothula, Jamie Redes, Ivan Reyes Torres, Mark P. Roberto, Alfonso R. Sanchez-Paulete, Joan Shang, Alessandra Soares Schanoski, Maria Suprun, Michelle Tran, Natalie Vaninov, C. Matthias Wilk, Julio A. Aguirre-Ghiso, Dusan Bogunovic1, Judy H. Cho, Jeremiah J. Faith, Emilie K. Grasset, Peter S. Heeger, Ephraim Kenigsberg, Florian Krammer1, Uri Laserson1 
16 Jun 2020-Immunity
TL;DR: The current state of knowledge of innate and adaptive immune responses elicited by SARS-CoV-2 infection and the immunological pathways that likely contribute to disease severity and death are summarized.

1,350 citations

Journal ArticleDOI
TL;DR: Key Clinical Points Evaluation and Management of Severe Covid-19 Patients with severe coronavirus disease 2019 (Covid- 19) may become critically ill with acute respiratory distress syndrome that typ...
Abstract: Key Clinical Points Evaluation and Management of Severe Covid-19 Patients with severe coronavirus disease 2019 (Covid-19) may become critically ill with acute respiratory distress syndrome that typ...

1,077 citations