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The standard of care for patients with stage III non-small-cell lung cancer (NSCLC) is concurrent chemoradiotherapy (CCRT) followed by 1 year of adjuvant durvalumab. Despite the survival benefit granted by immunotherapy in this setting, only 1/3 of patients are alive and disease free at 5 years. Novel treatment strategies are under development to improve patient outcomes in this setting: different anti-programmed cell death protein 1/programmed death-ligand 1 [anti-PD-(L)1] antibodies after CCRT, consolidation immunotherapy after sequential chemoradiotherapy, induction immunotherapy before CCRT and immunotherapy concurrent with CCRT and/or sequential chemoradiotherapy. Cross-trial comparison is particularly challenging in this setting due to the different timing of immunotherapy delivery and different patients' inclusion and exclusion criteria. In this review, we present the results of clinical trials investigating immune therapy in unresectable stage III NSCLC and discuss in-depth their biological rationale, their pitfalls and potential benefits. Particular emphasis is placed on the potential mechanisms of synergism between chemotherapy, radiation therapy and different monoclonal antibodies, and how this affects the tumor immune microenvironment. The designs and questions tackled by ongoing clinical trials are also discussed. Last, we address open questions and unmet clinical needs, such as the necessity for predictive biomarkers (e.g. radiomics and circulating tumor DNA). Identifying distinct subsets of patients to tailor anticancer treatment is a priority, especially in a heterogeneous disease such as stage III NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiorradioterapia/métodos , Humanos , Fatores Imunológicos , Imunoterapia/métodos , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Microambiente TumoralRESUMO
The COVID-19 pandemic poses a major burden on healthcare and economic systems across the globe. Even though a majority of the population develops only minor symptoms upon SARS-CoV-2 infection, a significant number are hospitalized at intensive care units (ICU) requiring critical care. While insights into the early stages of the disease are rapidly expanding, the dynamic immunological processes occurring in critically ill patients throughout their recovery at ICU are far less understood. Here, we have analysed whole blood samples serially collected from 40 surviving COVID-19 patients throughout their recovery in ICU using high-dimensional cytometry by time-of-flight (CyTOF) and cytokine multiplexing. Based on the neutrophil-to-lymphocyte ratio (NLR), we defined four sequential immunotypes during recovery that correlated to various clinical parameters, including the level of respiratory support at concomitant sampling times. We identified classical monocytes as the first immune cell type to recover by restoration of HLA-DR-positivity and the reduction of immunosuppressive CD163 + monocytes, followed by the recovery of CD8 + and CD4 + T cell and non-classical monocyte populations. The identified immunotypes also correlated to aberrant cytokine and acute-phase reactant levels. Finally, integrative analysis of cytokines and immune cell profiles showed a shift from an initially dysregulated immune response to a more coordinated immunogenic interplay, highlighting the importance of longitudinal sampling to understand the pathophysiology underlying recovery from severe COVID-19.
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COVID-19/imunologia , Estado Terminal , Contagem de Leucócitos , SARS-CoV-2 , Proteínas de Fase Aguda/análise , Antígenos CD/análise , COVID-19/sangue , Convalescença , Citocinas/sangue , Feminino , Seguimentos , Antígenos HLA-DR/análise , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Contagem de Linfócitos , Subpopulações de Linfócitos , Masculino , Pessoa de Meia-Idade , Monócitos , Neutrófilos , Pandemias , Prognóstico , Estudos ProspectivosRESUMO
Human noroviruses (NoV) are the main pathogenic agents worldwide responsible for viral sporadic and epidemic gastroenteritis worldwide. A gastroenteritis outbreak broke out in patients hospitalized in several wards located in two different floors of a hospital in Liege, Belgium. The objective was to determine whether a same NoV strain would be involved in the two different floors, and to explore how this outbreak would have spread from a floor to the other. Stool samples from patients and healthcare workers were collected, as well as data from medical files. NoV detection, quantification and characterization were performed using molecular biology methods. A same NoV strain, from genotype GII.4, was detected in two patients hospitalized on the two different floors. This finding allowed to conclude that a same outbreak spread in the two floors, probably due to movements of common healthcare workers. A rapid NoV detection during outbreak is important in the aim to rapidly implement hygiene measures to limit the size of the outbreak.
Les norovirus humains (NoV) sont reconnus mondialement comme les principaux agents étiologiques de gastro-entérites virales sporadiques et épidémiques au niveau mondial. Une épidémie de gastro-entérites s'est déclarée chez des patients hospitalisés dans plusieurs salles d'un hôpital de la région liégeoise, situées à deux étages différents. L'objectif était de déterminer si une même souche de NoV était impliquée aux deux étages, et d'investiguer la manière dont l'épidémie se serait propagée d'un étage à l'autre. Des prélèvements ont été collectés chez les patients et le personnel soignant. Les dossiers médicaux ont été examinés. La détection, la quantification et la caractérisation des souches de NoV ont été réalisées par des méthodes de biologie moléculaire. Une même souche de NoV, du génotype GII.4, a été mise en évidence chez deux patients hospitalisés aux deux étages différents. Ce résultat indique qu'il s'agit de la même épidémie qui s'est étendue à deux étages, probablement transmise par l'intermédiaire du personnel soignant commun. L'identification précoce des NoV lors des épidémies est primordiale afin de mettre en place rapidement les mesures d'hygiène permettant de limiter leur propagation.
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Infecções por Caliciviridae , Infecção Hospitalar , Surtos de Doenças , Norovirus , Bélgica , Infecções por Caliciviridae/epidemiologia , Genótipo , Hospitais , Humanos , Norovirus/isolamento & purificação , Filogenia , Análise de Sequência de DNARESUMO
Several species of mealybugs infest various parts of bananas and plantains including foliage, fruits, rhizome and roots in all the major banana growing regions of India and cause moderate to occasionally serious damage but systematic attempts at documenting the mealybug pests of banana and their natural enemies are lacking in India. In this study, mealybugs infesting bananas and plantains in Tamil Nadu, South India, are documented along with their coccinellid predators and other natural enemies. The exotic Jack Beardsley mealybug, Pseudococcus jackbeardsleyi Gimpel & Miller, was found to be a major pest of banana bunches in all localities surveyed in Tamil Nadu and the grey pineapple mealybug, Dysmicoccus neobrevipes Beardsley, was a serious pest in some isolated pockets. Three coccinellids, Scymnus (Pullus) coccivora Ramakrishna Ayyar, Nephus regularis Sicard and Slipinskiscymnus saciformis (Motschulsky) were found to be the major predators of all species of mealybugs. Brumoides suturalis (Fabricius) was predatory on solenopsis mealybug (Phenacoccus solenopsis Tinsley) only and Hyperaspis maindroni Sicard was associated with solenopsis mealybug and pink pineapple mealybug (Dysmicoccus brevipes (Cockerell)). One new species, Scymnus (Pullus) spicatus sp. n., is described as a predator of Jack Beardsley mealybug and striped mealybug (Ferrisia virgata (Cockerell)). Scymnus (Pullus) syoitii Sasaji, 1971, a Japanese species, is recorded for the first time from India as a predator of banana root mealybugs in Tamil Nadu and on Planococcus citri (Risso) in Karnataka. Brief notes on the other natural enemies of banana mealybugs are also given with illustrations.
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Formigas , Besouros , Hemípteros , Musa , Animais , Índia , FrutasRESUMO
The prized Red banana, selected for superior qualities, demands strong genetic uniformity for successful clonal propagation and preservation. Ensuring this uniformity early in the growth of in vitro Red banana plants is essential, as gene mutations and chromosome rearrangements during tissue culture can jeopardize both cloning and germplasm conservation. In this situation, molecular markers play a pivotal role in confirming genetic stability. Thus the study aims to discover a marker that identifies tissue-cultured Red bananas from their virescent variants during initial sub-culturing. A marker linked to anthocyanin has been identified which effectively differentiated Red bananas from virescent variants and it was further validated in various banana cultivars, ornamental Musa species and their interspecific hybrids. The PCR-based marker showed remarkable specificity, discerning Red bananas from virescent variants during tissue culture. It also distinguished green and red offspring, cutting time and resource costs, and shortening the banana breeding cycle. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03868-6.
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Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae have been described worldwide, but there are few reports on the carriage of these bacteria in Cameroon. In order to investigate the types of ESBLs and to analyse some risk factors associated with ESBL carriage, faecal samples were collected between 3 January and 3 April 2009 from hospitalised patients at Yaounde Central Hospital and at two hospitals in Ngaoundere, Cameroon. Enterobacterial isolates resistant to third-generation cephalosporins were screened for ESBL production using the double-disk synergy test. Polymerase chain reaction (PCR) and DNA sequencing were performed in order to find out the different types of ESBL genes in presumptive ESBL-positive isolates. During the study period, a total of 121 different patients were screened for ESBL carriage. The prevalence among these patients whose faecal samples were found to contain ESBL-producers was 55.3 % (67/121). According to a univariate analysis, hospitalisation during the previous year was found to be associated with ESBL carriage. Of the 71 bacteria isolated, Escherichia coli was predominant and represented 48 % of all isolates. ESBL characterisation revealed two types of ESBLs, CTX-M-15 (96 %) and SHV-12 (4 %). The present study emphasises the importance of screening for ESBLs in laboratories in African countries. The monitoring and detection of ESBL-producing bacteria are important in the setting up of appropriate treatment of patients and to ensure effective infection control efforts.
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Portador Sadio/epidemiologia , Portador Sadio/microbiologia , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/enzimologia , beta-Lactamases/genética , Adulto , Idoso , Antibacterianos/farmacologia , Camarões/epidemiologia , Cefalosporinas/farmacologia , DNA Bacteriano/química , DNA Bacteriano/genética , Enterobacteriaceae/classificação , Enterobacteriaceae/isolamento & purificação , Fezes/microbiologia , Feminino , Hospitalização/estatística & dados numéricos , Hospitais , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prevalência , Análise de Sequência de DNA , beta-Lactamases/metabolismoRESUMO
BACKGROUND: Treatments aiming at slowing down the progression of Alzheimer's disease (AD) may soon become available. However, information about the risks that people are willing to accept in order to delay the progression of the disease is limited. OBJECTIVE: To determine the trade-offs that individuals are willing to make between the benefits and risks of hypothetical treatments for AD, and the extent to which these trade-offs depend on individuals' characteristics and beliefs about medicines. DESIGN: Online, cross-sectional survey study. SETTING: Population in the UK. Public link to the survey available at the websites of Alzheimer's Research UK and Join Dementia Research. PARTICIPANTS: Everyone self-reported ≥18 years old was eligible to participate. A total of 4384 people entered the survey and 3658 completed it. MEASUREMENTS: The maximum acceptable risks (MARs) of participants for moderate and severe adverse events in exchange for a 2-year delay in disease progression. The risks were expressed on ordinal scales, from <10% to ≥50%, above a pre-existing risk of 30% for moderate adverse events and 10% for severe adverse events. We obtained the population median MARs using log-normal survival models and quantified the effects of individuals' characteristics and beliefs about medicines in terms of acceleration factors. RESULTS: For the moderate adverse events, 26% of the participants had a MAR ≥50%, followed by 25% of the participants with a MAR of 10 to <20%, giving an estimated median MAR of 25.4% (95% confidence interval [CI] 24.5 to 26.3). For the severe adverse events, 43% of the participants had a MAR <10%, followed by 25% of the participants with a MAR of 10 to <20%, resulting in an estimated median MAR of 12.1% (95%CI 11.6 to 12.5). Factors that were associated with the individuals' MARs for one or both adverse events were age, gender, educational level, living alone, and beliefs about medicines. Whether or not individuals were living with memory problems or had experience as a caregiver had no effect on the MARs for any of the adverse events. CONCLUSION: Trade-offs between benefits and risks of AD treatments are heterogeneous and influenced by individuals' characteristics and beliefs about medicines. This heterogeneity should be acknowledged during the medicinal product decision-making in order to fulfil the needs of the various subpopulations.
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Doença de Alzheimer , Humanos , Adolescente , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/complicações , Estudos Transversais , Inquéritos e QuestionáriosRESUMO
Objectives AmpC ß-lactamases are cephalosporinases that confer resistance to cephalothin, cefazolin, cefoxitin, penicillin, and ß-lactamase inhibitor-ß-lactam combinations. Even though the AmpC resistance is reported, but the accurate occurrence of AmpC ß-lactamases in Enterobacteriaceae members is still unknown. Techniques to identify AmpC producers are still evolving but not yet optimized for the clinical laboratory. Here we aimed to compare the test performance of two different phenotypic methods, that is inhibitor-based assay using boronic acid and disk approximation test for AmpC detection in Enterobacteriaceae isolates from a tertiary hospital microbiology laboratory. Materials and Methods The study includes 137 nonrepeat Enterobacteriaceae strains. Bacterial isolates, that yielded a zone diameter of less than 18 mm for cefoxitin by disk diffusion method were considered potential AmpC producers and further confirmed by phenotype methods-inhibitor-based assay using boronic acid and disk approximation test. A multiplex polymerase chain reaction was used to detect the most common plasmid-mediated AmpC genes: ACC, FOX, MOX, DHA, CIT, and EBC. Results Of the 137 clinical isolates, 58 (42.33%) were cefoxitin resistant, while 53.4 and 18.9% of the cefoxitin-resistant isolates were positive by inhibitor-based assay and disk approximation test. Multiplex PCR detected 42 (30.6%) isolates with AmpC genes. Of the 42 isolates, the inhibitor-based assay detected 25 (59.5%) isolates, while the disk approximation test detected nine (21.4%) isolates. Conclusion Our findings suggest that inhibitor-based assay using boronic acid can be used for the detection of the isolates that harbor AmpC ß-lactamases. This method is cost-effective, simple to perform, and easy to interpret. Thus AmpC detection as a routine in clinical laboratories can help in appropriate therapeutic intervention and improved infection control.
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We report circularly polarised emission, with helicity opposite to the optical excitation, from a van der Waals heterostructure (HS) consisting of a monolayer MoS2 and three-layer WS2. Selective excitation of the MoS2 layer confirms that this cross-polarized emission is due to the charge transfer from the WS2 layers to the MoS2 layer. We propose that the high levels of n-doping in the constituent layers due to sulphur vacancies and defects give rise to an enhanced transition rate of electrons from the k valley of WS2 to the k' valley of MoS2, which leads to the emission, counter polarized to the excitation. Simulations based on the rate equation model support this conclusion.
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OBJECTIVE: SARS CoV-2 is an epidemic viral infection that can cause mild to severe lung involvement. Newly apprehended knowledge on thoracic imaging abnormalities and the growing clinical experience on the evolution of this disease make the radiographic follow-up of hospitalized patients relevant. The value of consecutive bedside lung ultrasonography in the follow-up of hospitalized patients with SARS CoV-2 pneumonia and its correlation with other clinical and laboratory markers needs to be evaluated. METHODS: We assessed 39 patients [age: 64 y(60.1-68.7)] with confirmed SARS CoV-2 pneumonia. A total of 24 patients were hospitalized until the follow-up test, 9 were discharged early and 6 required a transfer to critical care unit. Two ultrasound scans of the lung were performed on day 1 and 4 of patients' hospitalization. Primary endpoint was the magnitude of association between a global lung ultrasound score (LUS) and clinical and laboratory markers. Secondary endpoint was the association between the evolution of LUS with the corresponded changes in clinical and laboratory outcomes during hospitalization period. RESULTS: LUS score on admission was higher among the deteriorating patients and significantly (P=0.038-0.0001) correlated (Spearman's rho) with the levels of C-reactive protein (0.58), lymphocytes (-0.33), SpO2 (-0.48) and oxygen supplementation (0.48) upon admission. The increase in LUS score between the two scans was significantly correlated (0.544, P=0.006) with longer hospital stay. CONCLUSION: Lung ultrasound assessment can be a useful as an imaging modality for SARS CoV-2 patients. Larger studies are needed to further investigate the predictive role of LUS in the duration and the outcome of the hospitalization of these patients.
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COVID-19 , Pneumonia , Hospitalização , Humanos , Pulmão/diagnóstico por imagem , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , SARS-CoV-2 , UltrassonografiaRESUMO
Epidemiological and clinical reports indicate that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate the immunopathology underlying COVID-19 severity, we perform cytokine and multiplex immune profiling in COVID-19 patients. We show that hypercytokinemia in COVID-19 differs from the interferon-gamma-driven cytokine storm in macrophage activation syndrome, and is more pronounced in critical versus mild-moderate COVID-19. Systems modelling of cytokine levels paired with deep-immune profiling shows that classical monocytes drive this hyper-inflammatory phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8+ cells being disproportionately affected. Antigen presenting machinery expression is also reduced in critical disease. Furthermore, we report that neutrophils contribute to disease severity and local tissue damage by amplification of hypercytokinemia and the formation of neutrophil extracellular traps. Together our findings suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity.
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COVID-19/complicações , COVID-19/imunologia , Síndrome da Liberação de Citocina/complicações , Monócitos/patologia , Ativação de Neutrófilo , Idoso , Células Apresentadoras de Antígenos/imunologia , COVID-19/sangue , COVID-19/virologia , Estudos de Casos e Controles , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/patologia , Síndrome da Liberação de Citocina/virologia , Citocinas/sangue , Armadilhas Extracelulares/metabolismo , Feminino , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/fisiologia , Índice de Gravidade de DoençaRESUMO
The major application of MALDI-TOF mass spectrometry in clinical microbiology is the bacterial identification based on the analysis of all their proteins (ribosomal and membrane-associated proteins). This technology allows the identification of most of bacteria within a few minutes. The method is fast, accurate, reliable and cost-effective by comparison to conventional phenotypic techniques. Other applications of MALDI-TOF mass spectrometry are still under development, as the detection of bacterial toxins or resistance mechanisms to antimicrobial agents.
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Bactérias/química , Infecções Bacterianas/diagnóstico , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Bactérias/isolamento & purificação , HumanosRESUMO
The CAL1 gene was cloned by complementation of the defect in Calcofluor-resistant calR1 mutants of Saccharomyces cerevisiae. Transformation of the mutants with a plasmid carrying the appropriate insert restored Calcofluor sensitivity, wild-type chitin levels and normal spore maturation. Southern blots using the DNA fragment as a probe showed hybridization to a single locus. Allelic tests indicated that the cloned gene corresponded to the calR1 locus. The DNA insert contains a single open-reading frame encoding a protein of 1,099 amino acids with a molecular mass of 124 kD. The predicted amino acid sequence shows several regions of homology with those of chitin synthases 1 and 2 from S. cerevisiae and chitin synthase 1 from Candida albicans. calR1 mutants have been found to be defective in chitin synthase 3, a trypsin-independent synthase. Transformation of the mutants with a plasmid carrying CAL1 restored chitin synthase 3 activity; however, overexpression of the enzyme was not achieved even with a high copy number plasmid. Since Calcofluor-resistance mutations different from calR1 also result in reduced levels of chitin synthase 3, it is postulated that the products of some of these CAL genes may be limiting for expression of the enzymatic activity. Disruption of the CAL1 gene was not lethal, indicating that chitin synthase 3 is not an essential enzyme for S. cerevisiae.
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Quitina Sintase/genética , Proteínas Fúngicas/genética , Genes Fúngicos , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Sequência de Aminoácidos , Sequência de Bases , Southern Blotting , Quitina Sintase/metabolismo , Clonagem Molecular , Dados de Sequência Molecular , Mutação , Plasmídeos , Saccharomyces cerevisiae/enzimologia , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , Transformação GenéticaRESUMO
The morphology of three Saccharomyces cerevisiae strains, all lacking chitin synthase 1 (Chs1) and two of them deficient in either Chs3 (calR1 mutation) or Chs2 was observed by light and electron microscopy. Cells deficient in Chs2 showed clumpy growth and aberrant shape and size. Their septa were very thick; the primary septum was absent. Staining with WGA-gold complexes revealed a diffuse distribution of chitin in the septum, whereas chitin was normally located at the neck between mother cell and bud and in the wall of mother cells. Strains deficient in Chs3 exhibited minor abnormalities in budding pattern and shape. Their septa were thin and trilaminar. Staining for chitin revealed a thin line of the polysaccharide along the primary septum; no chitin was present elsewhere in the wall. Therefore, Chs2 is specific for primary septum formation, whereas Chs3 is responsible for chitin in the ring at bud emergence and in the cell wall. Chs3 is also required for chitin synthesized in the presence of alpha-pheromone or deposited in the cell wall of cdc mutants at nonpermissive temperature, and for chitosan in spore walls. Genetic evidence indicated that a mutant lacking all three chitin synthases was inviable; this was confirmed by constructing a triple mutant rescued by a plasmid carrying a CHS2 gene under control of a GAL1 promoter. Transfer of the mutant from galactose to glucose resulted in cell division arrest followed by cell death. We conclude that some chitin synthesis is essential for viability of yeast cells.
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Quitina Sintase/metabolismo , Saccharomyces cerevisiae/enzimologia , Divisão Celular , Parede Celular/química , Parede Celular/ultraestrutura , Quitina/análise , Quitina/biossíntese , Microscopia Eletrônica , Mutação , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Saccharomyces cerevisiae/ultraestruturaRESUMO
Serology is currently used for the diagnosis of canine sino-nasal aspergillosis (SNA). However, the accuracy of serological testing using commercially available, standardized purified antigen preparations of Aspergillus (CAPurAspAg) has only been poorly documented. The aim of the present study was to assess the diagnostic value of an agar-gel double immunodiffusion (AGDD) test and an anti-Aspergillus IgG ELISA, using CAPurAspAg and the commercially available Platelia test for the detection of serum galactomannan. Sera from 17 dogs with SNA, 18 dogs with a nasal tumour (NT), 11 dogs with lymphoplasmacytic rhinitis (LPR) and 33 control dogs were tested with the 3 methods. AGDD result was positive in 76.5% of dogs with SNA, whereas all sera from dogs with non-fungal nasal disease and control dogs were negative. A positive IgG ELISA result was obtained in 88% of dogs with SNA and in 18% of dogs with LPR. All patients with NT and control dogs had a negative IgG ELISA result. The Platelia test was positive in 24% of dogs with SNA, 11% of dogs with NT, 9% of dogs with LPR and 24% of control dogs. The results of this study suggest that (1) the detection of serum Aspergillus-specific antibodies with AGDD or ELISA, using CAPurAspAg, provides excellent specificity and good sensitivity, (2) the specificity is higher for AGDD (100%) than for ELISA (96.8%) while sensitivity is higher for ELISA (88.2%) than for AGDD (76.5%) and (3) serum galactomannan quantification with the Plateliat test is unreliable for the diagnosis of canine SNA.
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Anticorpos Antifúngicos/sangue , Aspergilose/veterinária , Aspergillus/imunologia , Doenças do Cão/diagnóstico , Mananas/sangue , Doenças Nasais/veterinária , Sinusite/veterinária , Animais , Aspergilose/sangue , Aspergilose/imunologia , Doenças do Cão/microbiologia , Cães , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Galactose/análogos & derivados , Imunoglobulina G/sangue , Masculino , Doenças Nasais/diagnóstico , Doenças Nasais/microbiologia , Sinusite/diagnóstico , Sinusite/microbiologiaRESUMO
A 71-year-old male with mild steroid-induced hyperglycaemia was diagnosed with a lethal invasive Rhizopus microsporus infection. Disseminated zygomycosis is a rare entity and is most frequently found in neutropenic patients with haematological malignancies, post-transplants or in patients on deferoxamine therapy. Infection is characterised by tissue infarction and necrosis due to angioinvasive hyphae. Culture of Zygomycetes is necessary for species determination but histology is a must to prove the infection. Ante-mortem diagnosis and culture is challenging and therefore mortality approaches 100%. Apart from amphotericine B, most anti-fungals have no activity against Zygomycetes but posaconazole might offer new possibilities as a first-line agent. Timely diagnosis, rapid surgery of infected tissue, correction of underlying disorders and correct anti-fungal therapy might be life-saving. Due to the increasing use of potent immunosuppression, stem cell and organ transplants and possibly selection for Zygomycetes by prior treatment with broad-spectrum antifungal therapy, the incidence of zygomycosis is rising. Therefore, clinicians might encounter an increasing number of zygomycosis cases in the near future.
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Corticosteroides/efeitos adversos , Mucormicose/tratamento farmacológico , Rhizopus , Idoso , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios/efeitos adversos , Antifúngicos/uso terapêutico , Ciprofloxacina/uso terapêutico , Evolução Fatal , Humanos , Itraconazol/uso terapêutico , Masculino , Mucormicose/etiologia , Mucormicose/microbiologia , Prednisolona/efeitos adversos , Pirimidinas/uso terapêutico , Triazóis/uso terapêutico , VoriconazolRESUMO
BACKGROUND: Despite efforts to control human African trypanosomiasis (HAT) in the field, this infection remains prevalent in endemic or epidemic form in most of its traditional habitats. In the Democratic Republic of Congo (DRC), HAT has extended beyond rural areas to reach large cities such as Kinshasa. The objective of this study was to analyse the characteristics of trypanosomiasis patients (cases) in Kinshasa and to compare them to those of healthy controls. METHODS AND POPULATION OF STUDY: This case-control study allowed us to compare case patients and controls for some epidemiologic, clinical and sociodemographic characteristics. In all, 1764 people (588 case-patients and 1176 controls) were interviewed according to a structured questionnaire. Case-patients were infected with trypanosomiasis and entered the National Human African Trypanosomiasis Program (PNLTHA-DRC) from January 2004 through December 2005. Controls were matched for sex, age and residence to the corresponding case-patient, but had negative results from the Card Agglutination Trypanosomiasis Test (CATT-Test) whole-blood serologic analysis. Each patient was matched with two controls. RESULTS: Cases were identified in all 24 districts of Kinshasa, but were concentrated in the outskirts (outlying areas and southern expansion) and in rural areas. Overall, 25% (144/588) of case-patients lived in urbanized areas. People in the labour market (aged 20-49 years) were affected more often than others. HAT affected men and women equally. It also affected at higher rates people who moved around a lot and those who worked in rural or domestic activities, especially those in close contact with watercourses. Sleep disorders were the primary clinical sign (85%). Cervical adenopathies were observed frequently (66%). Fever was reported in 68% of case-patients. Most (73.5%) were diagnosed at a very advanced stage of infection (meningoencephalitic or neurological stage). CONCLUSION: These results highlight several modifiable or avoidable characteristics associated with HAT. Interventions on them might make it possible to reduce the morbidity and mortality rates associated with HAT and prevent wider extension of this disease.
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Tripanossomíase Africana/epidemiologia , Adulto , Fatores Etários , Testes de Aglutinação , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , República Democrática do Congo/epidemiologia , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores Sexuais , Fatores Socioeconômicos , Inquéritos e Questionários , Tripanossomíase Africana/diagnóstico , Tripanossomíase Africana/prevenção & controle , UrbanizaçãoRESUMO
UNLABELLED: Private dispensaries play an important role in the use of drugs such as antibiotics at community level. However, the knowledge and perceptions of staff working in these private dispensaries as regards bacterial resistance have not been sufficiently studied. OBJECTIVES: To assess the knowledge and perceptions of staff working in private dispensaries in Abidjan as regards bacterial resistance. MATERIALS AND METHODS: A survey was carried out among 123 members of staff working in private dispensaries, during a horizontal study conducted in 18 private dispensaries selected at random in the town of Abidjan in the Ivory Coast. Group meetings were also held to better understand the perceptions of staff working in these private dispensaries as regards bacterial resistance. RESULTS: Four antibiotics out of five bought in these private dispensaries in Abidjan were dispensed by pharmacy assistants. However, they were less informed than the pharmacists as regards bacterial resistance and the factors involved in its emergence. All the pharmacists interviewed in the study showed a good theoretical knowledge of bacterial resistance. However, the group meetings revealed that the risks of emergence of bacterial resistance in the case of antibiotics being dispensed without a prescription, and the threat of this resistance in terms of public health, were less perceived by the pharmacists. CONCLUSIONS: Assistants in dispensaries are less well-informed about bacterial resistance and the factors determining its emergence even though they dispense the most antibiotics to customers. Pharmacists have theoretical knowledge of bacterial resistance but are less conscious of its impact in terms of public health. Information campaigns on bacterial resistance are highly recommended as regards staff working in private dispensaries in Abidjan.
Assuntos
Farmacorresistência Bacteriana , Farmácias/organização & administração , Adulto , Antibacterianos/uso terapêutico , Côte d'Ivoire , Uso de Medicamentos , Feminino , Grupos Focais , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Farmacêuticos , Técnicos em Farmácia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The inappropriate dispensing of antibiotics and inadequate antibiotic treatment leads to the emergence of bacterial resistance. The aim of this study is to assess and describe the antibiotics dispensed upon the recommendation of staff in private pharmacies in Abidjan. It is also a matter of determining whether the information given when the drug is dispensed encourages the correct compliance of the antibiotic treatment by the patients. METHODS: Eighteen private pharmacies were in these private pharmacies was recorded using observation handbooks. Focus groups were set up with staff from the private pharmacies with the aim of better understanding of the actions observed. In the study, only antibiotics administered in systemic way were taken into account. RESULTS: One thousand one hundred and twenty-three purchases of antibiotics were observed in total, 158 of which were dispensed upon the recommendation of staff in the private pharmacies (14.1%) [95% CI = 12.1-16.3%]. Penicillin, co-trimoxazole and macrolides constituted the most frequently recommended groups of antibiotics. Compared with the assistants, the pharmacists recommended antibiotics more frequently to customers. The three main groups of symptoms leading to the dispensing of antibiotics upon recommendation were respiratory, gastro-intestinal and cutaneous symptoms. The staff in private pharmacies almost systematically recommended antibiotics for loose coughs lasting more than three days without taking into account the customer's age, general condition and extra-respiratory signs. The duration of the antibiotic treatment was clearly given in 25 cases (15.8%) and information telling customers to take antibiotics at mealtimes was only given on exceptional occasions. It transpired from the meetings conducted with pharmacy staff that there were indirect financial incentives, known as "Unités Gratuites", offered by the medical reps from certain pharmaceutical laboratories, encouraging the excessive dispensing of antibiotics. CONCLUSION: The staff in private pharmacies in Abidjan advise customers to take antibiotics even though they are prescription-only drugs. This leads to the inappropriate dispensing of antibiotics. Some information essential for the correct compliance of the treatment by patients, such as the duration of the treatment and taking it at mealtimes, are often omitted. Educational interventions aimed at pharmacy staff and measures encouraging the application of the law on the sale of antibiotics, are necessary to improve the dispensing of these drugs in private pharmacies in Abidjan.
Assuntos
Farmacorresistência Bacteriana , Farmácias/organização & administração , Adulto , Antibacterianos/uso terapêutico , Côte d'Ivoire , Uso de Medicamentos , Feminino , Grupos Focais , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Farmacêuticos , Técnicos em Farmácia , Inquéritos e QuestionáriosRESUMO
AIM OF THE STUDY: Nine plants from Reunion Island, selected using ethnopharmacology and chemotaxonomy, were investigated for their potential antimalarial value. MATERIALS AND METHODS: Thirty-eight extracts were prepared by maceration using CH(2)Cl(2) and MeOH, and were tested for in vitro activity against the 3D7 and W2 strain of Plasmodium falciparum. The most active extracts were then tested for in vitro cytotoxicity on human WI-38 fibroblasts to determine the selectivity index. Those extracts were also investigated in vivo against Plasmodium berghei infected mice. RESULTS: Most active of the extracts tested were the dichloromethane leaves extracts of Nuxia verticillata Lam. (Buddlejaceae), Psiadia arguta Voigt. (Asteraceae), Lantana camara L. (Verbenaceae), the methanol extracts from Aphloia theiformis (Vahl) Benn. (Aphloiaceae) bark, and Terminalia bentzoe L. (Combretaceae) leaves displaying in vitro IC(50) values ranging from 5.7 to 14.1mug/ml. Extracts from Psiadia, Aphloia at 200mg/(kgday) and Teminalia at 50mg/(kgday) also exhibited significant (p<0.0005) parasite inhibition in mice: 75.5%, 65.6% and 83.5%, respectively. CONCLUSION: Two plants showed interesting antimalarial activity with good selectivity: Aphloia theiformis and Terminalia bentzoe. Nuxia verticillata still needs to be tested in vivo, with a new batch of plant material.