Towards a standard protocol for antimony intralesional infiltration technique for cutaneous leishmaniasis treatment

BACKGROUND Despite its recognised toxicity, antimonial therapy continues to be the first-line drug for cutaneous leishmaniasis (CL) treatment. Intralesional administration of meglumine antimoniate (MA) represents an alternative that could reduce the systemic absorption of the drug and its side effects. OBJECTIVES This study aims to validate the standard operational procedure (SOP) for the intralesional infiltration of MA for CL therapy as the first step before the assessment of efficacy and safety related to the procedure. METHODS The SOP was created based on 21 trials retrieved from the literature, direct monitoring of the procedure and consultation with experts. This script was submitted to a formal computer-aided inspection to identify readability, clarity, omission, redundancy and unnecessary information (content validation). For criterion and construct validations, the influence of critical condition changes (compliance with the instructions and professional experience) on outcome conformity (saturation status achievement), tolerability (pain referred) and safety (bleeding) were assessed. FINDINGS The median procedure length was 12 minutes and in 72% of them, patients classified the pain as mild. The bleeding was also classified as mild in 96.6% of the procedures. Full compliance with the SOP was observed in 66% of infiltrations. Despite this, in 100% of the inspected procedures, lesion saturation was observed at the end of infiltration, which means that it tolerates some degree of modification in its execution (robustness) without prejudice to the result. CONCLUSIONS The procedure is reproducible and can be used by professionals without previous training with high success and safety rates

Mucosal leishmaniasis: the experience of a Brazilian referral center

Submitted by Nuzia Santos ([email protected]) on 2019-07-01T14:00:34Z No. of bitstreams: 1 Mucosal leishmaniasis.pdf: 4877215 bytes, checksum: d7ca5c9f2fd7210ab16f69421cf5541a (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2019-07-01T14:26:32Z (GMT) No. of bitstreams: 1 Mucosal leishmaniasis.pdf: 4877215 bytes, checksum: d7ca5c9f2fd7210ab16f69421cf5541a (MD5)Made available in DSpace on 2019-07-01T14:26:32Z (GMT). No. of bitstreams: 1 Mucosal leishmaniasis.pdf: 4877215 bytes, checksum: d7ca5c9f2fd7210ab16f69421cf5541a (MD5) Previous issue date: 2018Fundação Oswaldo Cruz. Instituto René Rachou. Pesquisa Clínica e Políticas Públicas em Doenças Infecciosas e Parasitárias. Belo Horizonte, MG, Brasil / Fundação Oswaldo Cruz. Instituto René Rachou. Programa de Pós-Graduação Stricto Sensu em Saúde Coletiva. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Pesquisa Clínica e Políticas Públicas em Doenças Infecciosas e Parasitárias. Belo Horizonte, MG, Brasil / Fundação Oswaldo Cruz. Instituto René Rachou. Programa de Pós-Graduação Stricto Sensu em Saúde Coletiva. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Pesquisa Clínica e Políticas Públicas em Doenças Infecciosas e Parasitárias. Belo Horizonte, MG, Brasil.Fundação Hospitalar do Estado de Minas Gerais. Hospital Eduardo de Menezes. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Pesquisa Clínica e Políticas Públicas em Doenças Infecciosas e Parasitárias. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Pesquisa Clínica e Políticas Públicas em Doenças Infecciosas e Parasitárias. Belo Horizonte, MG, Brasil.Fundação Hospitalar do Estado de Minas Gerais. Hospital Eduardo de Menezes. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Pesquisa Clínica e Políticas Públicas em Doenças Infecciosas e Parasitárias. Belo Horizonte, MG, Brasil / Fundação Oswaldo Cruz. Instituto René Rachou. Programa de Pós-Graduação Stricto Sensu em Saúde Coletiva. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Pesquisa Clínica e Políticas Públicas em Doenças Infecciosas e Parasitárias. Belo Horizonte, MG, Brasil / Fundação Oswaldo Cruz. Instituto René Rachou. Programa de Pós-Graduação Stricto Sensu em Saúde Coletiva. Belo Horizonte, MG, Brasil.INTRODUCTION: Pentavalent antimonials (Sbv) are the most commonly used drugs for the treatment of mucosal leishmaniasis (ML), despite their high toxicity and only moderate efficacy. The aim of this study was to report therapeutic responses with different available options for ML. METHODS: This study was based on a review of clinical records of 35 patients (24 men and 11 women) treated between 2009 and 2015. RESULTS: The median age of patients was 63 years, and the median duration of the disease was 24 months. Seventeen patients received Sbv, while nine patients were treated with liposomal amphotericin B (AmB), and another nine patients were treated with fluconazole. Patients treated with AmB received a total median accumulated dose of 2550mg. The mean duration of azole use was 120 days, and the daily dose ranged from 450 to 900mg. At the three-month follow-up visit, the cure rate was 35%, 67%, and 22% for Sbv, AmB, and azole groups, respectively. At the six-month follow-up visit, the cure rates for Sbv, AmB, and azole groups were 71%, 78%, and 33%, respectively. CONCLUSIONS: There is a scarcity of effective ML treatment alternatives, and based on our observations, fluconazole is not a valid treatment option

Towards a standard protocol for antimony intralesional infiltration technique for cutaneous leishmaniasis treatment

<div><p> BACKGROUND Despite its recognised toxicity, antimonial therapy continues to be the first-line drug for cutaneous leishmaniasis (CL) treatment. Intralesional administration of meglumine antimoniate (MA) represents an alternative that could reduce the systemic absorption of the drug and its side effects. OBJECTIVES This study aims to validate the standard operational procedure (SOP) for the intralesional infiltration of MA for CL therapy as the first step before the assessment of efficacy and safety related to the procedure. METHODS The SOP was created based on 21 trials retrieved from the literature, direct monitoring of the procedure and consultation with experts. This script was submitted to a formal computer-aided inspection to identify readability, clarity, omission, redundancy and unnecessary information (content validation). For criterion and construct validations, the influence of critical condition changes (compliance with the instructions and professional experience) on outcome conformity (saturation status achievement), tolerability (pain referred) and safety (bleeding) were assessed. FINDINGS The median procedure length was 12 minutes and in 72% of them, patients classified the pain as mild. The bleeding was also classified as mild in 96.6% of the procedures. Full compliance with the SOP was observed in 66% of infiltrations. Despite this, in 100% of the inspected procedures, lesion saturation was observed at the end of infiltration, which means that it tolerates some degree of modification in its execution (robustness) without prejudice to the result. CONCLUSIONS The procedure is reproducible and can be used by professionals without previous training with high success and safety rates.</p></div

Mucosal leishmaniasis: the experience of a Brazilian referral center

Abstract INTRODUCTION Pentavalent antimonials (Sbv) are the most commonly used drugs for the treatment of mucosal leishmaniasis (ML), despite their high toxicity and only moderate efficacy. The aim of this study was to report therapeutic responses with different available options for ML. METHODS This study was based on a review of clinical records of 35 patients (24 men and 11 women) treated between 2009 and 2015. RESULTS The median age of patients was 63 years, and the median duration of the disease was 24 months. Seventeen patients received Sbv, while nine patients were treated with liposomal amphotericin B (AmB), and another nine patients were treated with fluconazole. Patients treated with AmB received a total median accumulated dose of 2550mg. The mean duration of azole use was 120 days, and the daily dose ranged from 450 to 900mg. At the three-month follow-up visit, the cure rate was 35%, 67%, and 22% for Sbv, AmB, and azole groups, respectively. At the six-month follow-up visit, the cure rates for Sbv, AmB, and azole groups were 71%, 78%, and 33%, respectively. CONCLUSIONS There is a scarcity of effective ML treatment alternatives, and based on our observations, fluconazole is not a valid treatment option

Persistence of Yellow fever virus outside the Amazon Basin, causing epidemics in Southeast Brazil, from 2016 to 2018

<div><p>Background</p><p>Yellow fever (YF) is endemic in the Brazilian Amazon Basin, and sporadic outbreaks take place outside the endemic area in Brazil. Since 2016, YF epidemics have been occurring in Southeast Brazil, with more than 1,900 human cases and more than 1,600 epizooties of non-human primates (NHPs) reported until April 2018. Previous studies have demonstrated that Yellow fever virus (YFV) causing outbreaks in 2017 formed a monophyletic group.</p><p>Methodology/Principal findings</p><p>Aiming to decipher the origin of the YFV responsible for the recent epidemics, we obtained nucleotide sequences of YFV detected in humans (n = 6) and NHPs (n = 10) from Minas Gerais state during 2017–2018. Next, we performed evolutionary analyses and discussed the results in the light of epidemiological records (official numbers of YFV cases at each Brazilian Federative unit, reported by the Brazilian Ministry of Health). Nucleotide sequences of YFV from Southeast Brazil from 2016 to 2018 were highly conserved and formed a monophyletic lineage (BR-YFV_2016/18) within the genotype South America I. Different clusters were observed within lineage BR-YFV_2016/18, one containing the majority of isolates (from humans and NHPs), indicating the sylvatic transmission of YFV. We also detected a cluster characterized by two synapomorphies (amino acid substitutions) that contained YFV only associated with NHP what should be further investigated. The topology of lineage BR-YFV_2016/18 was congruent with epidemiological and temporal patterns of the ongoing epidemic. YFV isolates detected in 2016, in São Paulo state were located in the most basal position of the lineage, followed by the isolates from Minas Gerais and Espírito Santo obtained in 2017 and 2018. The most recent common ancestor of the lineage BR-YFV_2016/18 dated to 2015 (95% credible intervals = 2014–2016), in a period that was coincident with the reemergence of YFV in the Midwest region of Brazil.</p><p>Conclusions</p><p>The results demonstrated a single introduction of YFV in the Southeast region and the silent viral circulation before the onset of the outbreaks in 2016. Evolutionary analyses combined with epidemiological records supported the idea that BR-YFV_2016/18 was probably introduced from the Midwest into the Southeast region, possibly in São Paulo state. The persistence of YFV in the Southeast region, causing epidemics from 2016 to 2018, suggests that this region presents suitable ecological and climatic conditions for YFV maintenance during the epidemic and interepidemic seasons. This fact poses risks for the establishing of YF enzootic cycles and epidemics, outside the Amazon Basin in Brazil. YF surveillance and studies of viral dynamics deserve particular attention, especially in Midwest, Southeast and neighbor regions which are the main areas historically associated with YF outbreaks outside the Amazon Basin. YFV persistence in Southeast Brazil should be carefully considered in the context of public health, especially for public health decision-makers and researchers.</p></div

The ongoing COVID-19 epidemic in Minas Gerais, Brazil: insights from epidemiological data and SARS-CoV-2 whole genome sequencing.

The recent emergence of a previously unknown coronavirus (SARS-CoV-2), first confirmed in the city of Wuhan in China in December 2019, has caused serious public health and economic issues due to its rapid dissemination worldwide. Although 61,888 confirmed cases had been reported in Brazil by 28 April 2020, little was known about the SARS-CoV-2 epidemic in the country. To better understand the recent epidemic in the second most populous state in southeast Brazil (Minas Gerais, MG), we looked at existing epidemiological data from 3 states and sequenced 40 complete genomes from MG cases using Nanopore. We found evidence of multiple independent introductions from outside MG, both from genome analyses and the overly dispersed distribution of reported cases and deaths. Epidemiological estimates of the reproductive number using different data sources and theoretical assumptions all suggest a reduction in transmission potential since the first reported case, but potential for sustained transmission in the near future. The estimated date of introduction in Brazil was consistent with epidemiological data from the first case of a returning-traveler from Lombardia, Italy. These findings highlight the unique reality of MGs epidemic and reinforce the need for real-time and continued genomic surveillance strategies as a way of understanding and therefore preparing against the epidemic spread of emerging viral pathogens

The ongoing COVID-19 epidemic in Minas Gerais, Brazil: insights from epidemiological data and SARS-CoV-2 whole genome sequencing

The recent emergence of a coronavirus (SARS-CoV-2), first identified in the Chinese city of Wuhan in December 2019, has had major public health and economic consequences. Although 61,888 confirmed cases were reported in Brazil by 28 April 2020, little is known about the SARS-CoV-2 epidemic in this country. To better understand the recent epidemic in the second most populous state in southeast Brazil - Minas Gerais (MG) - we sequenced 40 complete SARS-CoV-2 genomes from MG cases and examined epidemiological data from three Brazilian states. Both the genome analyses and the geographical distribution of reported cases indicate for multiple independent introductions into MG. Epidemiological estimates of the reproductive number (R) using different data sources and theoretical assumptions suggest the potential for sustained virus transmission despite a reduction in R from the first reported case to the end of April 2020. The estimated date of SARS-CoV-2 introduction into Brazil was consistent with epidemiological data from the first case of a returned traveller from Lombardy, Italy. These findings highlight the nature of the COVID-19 epidemic in MG and reinforce the need for real-time and continued genomic surveillance strategies to better understand and prepare for the epidemic spread of emerging viral pathogens

Bayesian phylogenetic analyses of Yellow fever virus.

<p>The maximum clade credibility tree inferred using 60 Yellow fever virus sequences (1,038 nt) from South America is shown. The posterior probability values are represented by circles drawn in scale in the nodes. Clades containing Brazilian Yellow fever virus from outbreaks 2000–01, 2008–09 and the current (2016–2018) are shown in green, blue and red, respectively. Terminal branches in orange, pink and black represent sequences of Yellow fever virus from Venezuela, Bolivia, and Brazil, respectively. South African genotypes are collapsed in grey. Horizontal branch lengths are drawn to a scale of years. The tree was reconstructed using the nucleotide substitution model HKY with gamma distribution (four categories), under the relaxed molecular clock and Bayesian skyline demographic model. ES: Espírito Santo state, MG: Minas Gerais state and SP: São Paulo state. The asterisk (*) denotes the cluster of Yellow fever virus obtained from non-human primates which had two amino acid substitutions characterized as synapomorphies. Analyses were performed using programs from BEAST package v.1.8.4 [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006538#pntd.0006538.ref021" target="_blank">21</a>], BEAUTi v.1.8.2 [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006538#pntd.0006538.ref021" target="_blank">21</a>], Tracer v.1.5.0 [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006538#pntd.0006538.ref023" target="_blank">23</a>], TreeAnotator v.1.8.2 [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006538#pntd.0006538.ref024" target="_blank">24</a>] and FigTree v.1.4.3 [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006538#pntd.0006538.ref026" target="_blank">26</a>].</p