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1.
J Infect Chemother ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34598877

RESUMO

Lemierre's syndrome is a serious disease that typically causes oropharyngeal infection with internal jugular vein thrombosis, followed by distant infection focus, such as septic pulmonary embolism. The main causative organisms are anaerobic bacteria in the oral cavity, namely Fusobacterium necrophorum. We encountered an extremely rare case of Lemierre's syndrome, where double vision was found to be the first symptom. The patient's blood culture results showed the presence of F. nucleatum, which spread from the sphenoid sinus to the skull base because of chronic sinusitis; the patient presented with longus colli abscess, clivus osteomyelitis, venous thrombosis, and hematogenous infection. Antibiotic treatment with sulbactam/ampicillin was continued for 14 weeks, and no recurrence has been observed so far. Lemierre's syndrome can be complicated with atypical symptoms such as double vision if the cranial nerves are involved. It might be important to consider this disease in the differential diagnosis in the presence of cranial nerve symptoms of unknown origin with fever or inflammatory findings.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34574555

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Real-time RT-PCR is the most commonly used method for COVID-19 diagnosis. However, serological assays are urgently needed as complementary tools to RT-PCR. Hachim et al. 2020 and Burbelo et al. 2020 demonstrated that anti-nucleocapsid(N) SARS-CoV-2 antibodies are higher and appear earlier than the spike antibodies. Additionally, cross-reactive antibodies against N protein are more prevalent than those against spike protein. We developed a less cross-reactive immunoglobulin G (IgG) indirect ELISA by using a truncated recombinant SARS-CoV-2 N protein as assay antigen. A highly conserved region of coronaviruses N protein was deleted and the protein was prepared using an E. coli protein expression system. A total of 177 samples collected from COVID-19 suspected cases and 155 negative control sera collected during the pre-COVID-19 period were applied to evaluate the assay's performance, with the plaque reduction neutralization test and the commercial SARS-CoV-2 spike protein IgG ELISA as gold standards. The SARS-CoV-2 N truncated protein-based ELISA showed similar sensitivity (91.1% vs. 91.9%) and specificity (93.8% vs. 93.8%) between the PRNT and spike IgG ELISA, as well as also higher specificity compared to the full-length N protein (93.8% vs. 89.9%). Our ELISA can be used for the diagnosis and surveillance of COVID-19.


Assuntos
COVID-19 , Proteínas do Nucleocapsídeo , Anticorpos Antivirais , Teste para COVID-19 , Ensaio de Imunoadsorção Enzimática , Escherichia coli , Humanos , Imunoglobulina G , Proteínas do Nucleocapsídeo/genética , SARS-CoV-2 , Sensibilidade e Especificidade , Glicoproteína da Espícula de Coronavírus
4.
Respir Investig ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34531175

RESUMO

BACKGROUND: This study aimed to clarify the involvement of anaerobes in aspiration pneumonia by measuring volatile sulfur compounds (VSCs), which are metabolites of anaerobic bacteria in the mouth. METHODS: This study included 84 older adult patients (mean age, 82.5 ± 7.34 years) who had dementia and were hospitalized for more than 6 months. We measured the VSCs in the patient's mouth with Oral Chroma and obtained the data of pneumonia development in the past 6 months. We also evaluated the association or correlation of VSCs and some factors which might be the risk factors of aspiration pneumonia. RESULTS: The development of pneumonia had no significant association with the VSCs in the patient's mouth. CONCLUSION: The present pilot study suggests that anaerobes might not be the main causative pathogens of aspiration pneumonia in older adult patients.

5.
J Clin Med ; 10(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34441847

RESUMO

The relationship between microorganisms present in the lower respiratory tract and the subsequent incidence of pneumonia in patients with rheumatoid arthritis is unclear. A retrospective cohort study was designed to include a total of 121 patients with rheumatoid arthritis who underwent bronchoscopy at three hospitals between January 2008 and December 2017. Data on patient characteristics, microorganisms detected by bronchoscopy, and subsequent incidences of pneumonia were obtained from electronic medical records. Patients were divided into groups based on the microorganisms isolated from the lower respiratory tract. The cumulative incidence of pneumonia was assessed using the Kaplan-Meier method, and decision tree analysis was performed to analyze the relation between the presence of microorganisms and the occurrence of pneumonia. The most frequently isolated microbes were Pseudomonas aeruginosa, Staphylococcus aureus, and Haemophilus influenzae. Patients whose samples tested negative for bacteria or positive for normal oral flora were included in the control group. The rate of the subsequent incidence of pneumonia was higher in the P. aeruginosa group than in the control group (p = 0.026), and decision tree analysis suggested that P. aeruginosa and patient performance status were two important factors for predicting the incidence of pneumonia. In patients with rheumatoid arthritis, the presence of P. aeruginosa in the lower respiratory tract was associated with the subsequent incidence of pneumonia.

6.
J Infect Chemother ; 27(10): 1525-1528, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34294531

RESUMO

Polymerase chain reaction (PCR) testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is necessary for confirming a diagnosis of Coronavirus disease 2019 (COVID-19). Here we present a COVID-19 case of an elderly woman whose SARS-CoV-2 PCR tests showed false negative repeatedly by evaluating with different sampling sites and procedures. Nasopharyngeal swabs, suctioned sputum, and tongue swabs were collected for SARS-CoV-2-PCR. As for tongue swabs, we compared between two different sample conditions; one obtained with dry condition and the other obtained with moistened condition inside the oral cavity. SARS-CoV-2-PCR showed positive for an extended period with suctioned sputum samples compared with nasopharyngeal swabs and tongue swabs. No SARS-CoV-2 from a nasopharyngeal swab sample obtained on day 46 after symptoms onset was isolated despite high viral load (183740.5 copies/5µL). An adequate production of neutralizing antibody in a serum sample on day 46 was also confirmed. The number of RNA copies of the tongue swab samples was higher with moistened condition than with dry condition. The present case suggests that the difference of sampling site or sample condition can affect PCR results. High loads viral RNA detection does not always correlate with infectivity.


Assuntos
COVID-19 , SARS-CoV-2 , Idoso , Feminino , Humanos , Nasofaringe , Reação em Cadeia da Polimerase , RNA Viral , Manejo de Espécimes
7.
BMC Infect Dis ; 21(1): 573, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34126952

RESUMO

BACKGROUND: The recent increase in cases of azole-resistant Aspergillus fumigatus (ARAf) infections is a major clinical concern owing to its treatment limitations. Patient-derived ARAf occurs after prolonged azole treatment in patients with aspergillosis and involves various cyp51A point mutations or non-cyp51A mutations. The prognosis of patients with chronic pulmonary aspergillosis (CPA) with patient-derived ARAf infection remains unclear. In this study, we reported the case of a patient with ARAf due to HapE mutation, as well as the virulence of the isolate. CASE PRESENTATION: A 37-year-old male was presented with productive cough and low-grade fever. The patient was diagnosed with CPA based on the chronic course, presence of a fungus ball in the upper left lobe on chest computed tomography (CT), positivity for Aspergillus-precipitating antibody and denial of other diseases. The patient underwent left upper lobe and left S6 segment resection surgery because of repeated haemoptysis during voriconazole (VRC) treatment. The patient was postoperatively treated with VRC for 6 months. Since then, the patient was followed up without antifungal treatment but relapsed 4 years later, and VRC treatment was reinitiated. Although an azole-resistant isolate was isolated after VRC treatment, the patient did not show any disease progression in either respiratory symptoms or radiological findings. The ARAf isolated from this patient showed slow growth, decreased biomass and biofilm formation in vitro, and decreased virulence in the Galleria mellonella infection model compared with its parental strain. These phenotypes could be caused by the HapE splice site mutation. CONCLUSIONS: This is the first to report a case demonstrating the clinical manifestation of a CPA patient infected with ARAf with a HapE splice site mutation, which was consistent with the in vitro and in vivo attenuated virulence of the ARAf isolate. These results imply that not all the ARAf infections in immunocompetent patients require antifungal treatment. Further studies on the virulence of non-cyp51A mutations in ARAf are warranted.


Assuntos
Aspergillus fumigatus/genética , Azóis/farmacologia , Farmacorresistência Fúngica/efeitos dos fármacos , Proteínas Fúngicas/genética , Aspergilose Pulmonar/microbiologia , Adulto , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/isolamento & purificação , Aspergillus fumigatus/patogenicidade , Azóis/uso terapêutico , Doença Crônica , Humanos , Masculino , Testes de Sensibilidade Microbiana , Mutação , Fenótipo , Aspergilose Pulmonar/tratamento farmacológico , Virulência/genética , Voriconazol/uso terapêutico
8.
J Infect Chemother ; 27(7): 1033-1038, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33781691

RESUMO

INTRODUCTION: Numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests exists commercially; however, their performance using clinical samples is limited. Although insufficient to detect SARS-CoV-2 in the early phase of infection, antibody assays can be of great use for surveillance studies or for some coronavirus disease 2019 (COVID-19) patients presenting late to the hospital. METHODS: This study evaluated the sensitivity and specificity of four commercial SARS-CoV-2 lateral flow antibody tests using 213 serum specimens from 90 PCR-positive confirmed COVID-19 patients. Of 59 negative control sera, 50 were obtained from patients with other respiratory infectious diseases before COVID-19 pandemic began while nine were from patients infected with other respiratory viruses, including two seasonal coronaviruses. RESULTS: The varied sensitivities for the four commercial kits were 70.9%, 65.3%, 45.1%, and 65.7% for BioMedomics, Autobio Diagnostics, Genbody, and KURABO, respectively, between sick days 1 and 155 in COVID-19 patients. The sensitivities of the four tests gradually increased over time after infection before sick day 5 (15.0%, 12.5%, 15.0%, and 20.0%); from sick day 11-15 (95.7%, 87.2%, 53.2%, and 89.4%); and after sick day 20 (100%, 100%, 68.6%, and 96.1%), respectively. For severe illness, the sensitivities were quite high in the late phase after sick day 15. The specificities were over 96% for all four tests. No cross-reaction due to other pathogens, including seasonal coronaviruses, was observed. CONCLUSIONS: Our results demonstrated the large differences in the antibody test performances. This ought to be considered when performing surveillance analysis.


Assuntos
COVID-19 , Pandemias , Anticorpos Antivirais , Humanos , Imunoglobulina M , SARS-CoV-2 , Sensibilidade e Especificidade , Testes Sorológicos
9.
Clin Case Rep ; 9(2): 707-710, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33598229

RESUMO

The treatment duration for candidemia with septic pulmonary embolism should be determined based on the clearance of fungus from the bloodstream and improvement of symptoms. The remaining lung nodules may not necessarily indicate persistent infection.

10.
Int J Infect Dis ; 103: 33-36, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33217572

RESUMO

A 60-year-old Japanese woman presented with subacute progressive muscle pain and weakness in her proximal extremities. She was diagnosed with influenza A (H3N2) infection a week before the onset of muscle pain. At the time of admission, she exhibited weakness in the proximal muscles of the upper and lower limbs, elevated serum liver enzymes and creatinine kinase, and myoglobinuria. She did not manifest renal failure and cardiac abnormalities, indicating myocarditis. Electromyography revealed myogenic changes, and magnetic resonance imaging of the upper limb showed abnormal signal intensities in the muscles, suggestive of myopathy. Muscle biopsy of the biceps revealed numerous necrotic regeneration fibers and mild inflammatory cell infiltration, suggesting immune-mediated necrotizing myopathy (IMNM). Necrotized muscle cells were positive for human influenza A (H3N2). Autoantibody analysis showed the presence of antibodies against the signal recognition particle (SRP), and the patient was diagnosed with anti-SRP-associated IMNM. She was resistant to intravenous methylprednisolone pulse therapy but recovered after administration of oral systemic corticosteroids and immunoglobulins. We speculate that the influenza A (H3N2) infection might have triggered her IMNM. Thus, IMNM should be considered as a differential diagnosis in patients with proximal muscle weakness that persists after viral infections.


Assuntos
Doenças Autoimunes/diagnóstico , Doenças Autoimunes/microbiologia , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Influenza Humana/complicações , Doenças Musculares/diagnóstico , Doenças Musculares/microbiologia , Partícula de Reconhecimento de Sinal/imunologia , Autoanticorpos/análise , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Influenza Humana/diagnóstico , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Doenças Musculares/imunologia , Doenças Musculares/patologia , Mialgia/diagnóstico , Necrose
11.
J Infect Chemother ; 27(3): 537-539, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33309631

RESUMO

OBJECTIVE: To evaluate the annual variation in the frequency of patient-acquired azole-resistant Aspergillus fumigatus (ARAf), and correlate it to the amount of oral triazole prescribed, in Nagasaki, Japan. METHODS: A. fumigatus isolates from respiratory specimens collected in the Nagasaki University Hospital (NUH) between 1996 and 2017 were included in the study. The amount of oral triazole prescribed in NUH since 2001 was obtained from the medical ordering system. Mutations in cyp51A, hmg1, and erg6 genes of ARAf were also analysed. RESULTS: From a total of 240 ARAf strains, 12 (5%), 6 (2.5%), 15 (6.25%), and 3 (1.25%) strains were resistant to itraconazole (ITC), voriconazole (VRC), to either ITC or VRC, and both triazoles, respectively. The amount of prescribed VRC increased annually, and was three times as large as that of ITC in 2017. All eleven patients harbouring ITC-resistant strains had a history of prior ITC treatment, while only one of six patients harbouring VRC-resistant strains had a history of prior VRC treatment. cyp51A mutations were recorded in 10 strains; however, tandem repeat mutations of the promoter region of cyp51A were not observed. Several azole-resistant strains had non-cyp51A mutations. CONCLUSIONS: The frequency of patient-acquired ARAf is not increasing in Nagasaki, Japan. Furthermore, the prevalence of VRC-induced ARAf was rare despite the remarkable increase in the amount of prescribed VRC. Mutations in genes other than cyp51A should also be considered when ARAf strains are obtained from patients treated with azole antifungals.


Assuntos
Aspergillus fumigatus , Triazóis , Antifúngicos/farmacologia , Aspergillus fumigatus/genética , Azóis/farmacologia , Sistema Enzimático do Citocromo P-450/genética , Farmacorresistência Fúngica/genética , Proteínas Fúngicas/genética , Humanos , Japão/epidemiologia , Testes de Sensibilidade Microbiana , Centros de Atenção Terciária , Triazóis/farmacologia
12.
Med Mycol ; 2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33369648

RESUMO

Pneumocystis jirovecii pneumonia (PCP) is an opportunistic and life-threatening pulmonary infection with an increasing prevalence among individuals who are human immunodeficiency virus (HIV)-negative. Evidence regarding diagnostic testing of PCP in this patient population is insufficient. We evaluated the performance of serum (1, 3)-ß-d-glucan (BDG) using the Fungitec G-test MK kit for diagnosing PCP in non-HIV patients. We retrospectively analyzed data from 219 non-HIV adult patients who underwent bronchoscopy and were tested for P. jirovecii DNA by PCR using lavage samples from the lower respiratory tract. Fifty PCP patients and 125 non-PCP patients were included. The most common underlying diseases were malignancies and systemic autoimmune diseases. Using the serum BDG Fungitec G-test MK test to diagnose PCP, the area under the receiver operating characteristic curve (AUC) was 0.924, whereas the modified cut-off value of 36.6 pg/mL had a sensitivity and specificity of 92.0% and 84.8%, respectively. The AUC for patients with systemic autoimmune diseases was 0.873, and the accuracy of serum BDG test declined when using methotrexate (MTX). In conclusion, the serum BDG test was useful for diagnosing PCP in non-HIV patients; however, the results should be carefully interpreted in case of MTX administration. LAY SUMMARY: The Fungitec G-test MK kit for measuring serum (1, 3)-ß-d-glucan (BDG) levels had a sufficient diagnostic performance for Pneumocystis jirovecii pneumonia (PCP) in human immunodeficiency virus-negative patients. However, the results should be carefully interpreted in case of MTX administration.

13.
Sci Rep ; 10(1): 17745, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33082485

RESUMO

Echinocandins, including caspofungin, micafungin, and anidulafungin, are first-line antifungal agents for the treatment of invasive candidiasis. They exhibit fungicidal activity by inhibiting the synthesis of ß-1,3-D-glucan, an essential component of the fungal cell wall. However, they are active only against proliferating fungal cells and unable to completely eradicate fungal cells even after a 24 h drug exposure in standard time-kill assays. Surprisingly, we found that caspofungin, when dissolved in low ionic solutions, had rapid and potent antimicrobial activities against multidrug-resistant (MDR) Candida and bacteria cells even in non-growth conditions. This effect was not observed in 0.9% NaCl or other ion-containing solutions and was not exerted by other echinocandins. Furthermore, caspofungin dissolved in low ionic solutions drastically reduced mature biofilm cells of MDR Candida auris in only 5 min, as well as Candida-bacterial polymicrobial biofilms in a catheter-lock therapy model. Caspofungin displayed ion concentration-dependent conformational changes and intracellular accumulation with increased reactive oxygen species production, indicating a novel mechanism of action in low ionic conditions. Importantly, caspofungin dissolved in 5% glucose water did not exhibit increased toxicity to human cells. This study facilitates the development of new therapeutic strategies in the management of catheter-related biofilm infections.


Assuntos
Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Candida/efeitos dos fármacos , Caspofungina/farmacologia , Bactérias/efeitos dos fármacos , Linhagem Celular , Humanos , Testes de Sensibilidade Microbiana , Preparações Farmacêuticas
14.
Acta Med Okayama ; 74(5): 407-413, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33106696

RESUMO

Endoscopic submucosal dissection (ESD) has become the first-line treatment for early gastric neoplasms; however, a subset of patients treated by this method develop aspiration pneumonia. We conducted a comprehensive prospective analysis of the factors contributing to post-ESD aspiration pneumonia in early gastric neoplasms in this study, with special focus on whether pre-treatment oral care can prevent aspiration pneumonia. Sixty-one patients who underwent ESD for gastric neoplasms were randomly assigned to the oral care or control groups. ESD was performed under deep sedation. Of 60 patients whose data were available for analysis, 5 (8.3%) experienced pneumonia confirmed either by chest radiography or computed tomography. Although no difference in the rate of pneumonia was found between the control and oral care groups, the post-oral care bacteria count was significantly higher in the saliva of patients who developed pneumonia compared to those without pneumonia. In addition, the presence of vascular brain diseases and the dose of meperidine were also significantly associated with the occurrence of pneumonia. These results suggest that the number of oral bacteria as well as pre-existing vascular brain diseases and high-dose narcotics can affect the incidence of post-ESD pneumonia.


Assuntos
Ressecção Endoscópica de Mucosa/efeitos adversos , Pneumonia Aspirativa/etiologia , Neoplasias Gástricas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Sedação Profunda/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Higiene Bucal/estatística & dados numéricos , Pneumonia Aspirativa/epidemiologia , Estudos Prospectivos , Fatores de Risco , Saliva/microbiologia
15.
Emerg Microbes Infect ; 9(1): 2266-2268, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32990189

RESUMO

A 68-year-old Japanese man was admitted to our hospital for an acute febrile illness with shivering and impaired consciousness. He was a previous smoker and had a history of chronic obstructive pulmonary disease, for which he inhaled steroid with a long-acting bronchodilator. He had received a 23-valent pneumococcal polysaccharide vaccination 2 years previously. He was intubated and placed on a ventilator in intensive care unit because of acute respiratory failure and hypercapnia. Streptococcus pneumoniae was grown from his blood, sputum, and urine cultures, and he was diagnosed with invasive pneumococcal disease with acute renal failure. He was treated with intravenous beta-lactam and macrolide with continuous hemodiafiltration and was discharged 3 months later. The pneumococcus was identified as serotype 12F, and his serotype-specific IgG and opsonophagocytic index against serotype 12F indicating a lack of protection from IPD among PPV23 serotypes. This case highlights that some individuals may have a serotype-specific polysaccharide antibody failure that makes them susceptible to serotype 12F invasive pneumococcal disease. This case also illustrates the need for serotype-specific IgG and opsonophagocytic index titre cut-offs for each specific pneumococcal serotype in available vaccines to understand the vaccination protection for individual patients better.


Assuntos
Antibacterianos/uso terapêutico , Infecções Pneumocócicas/diagnóstico , Infecções Pneumocócicas/imunologia , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/imunologia , Idoso , Anticorpos Antibacterianos/sangue , Hospitalização , Humanos , Masculino , Infecções Pneumocócicas/tratamento farmacológico , Sorotipagem , Streptococcus pneumoniae/isolamento & purificação , Vacinação
16.
Respir Investig ; 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32631765

RESUMO

BACKGROUND: Before advance care planning, it is essential to understand the differences in preferences for medical care of terminal-phase pneumonia in elderly patients among the patients, their families, and their doctors. This study aimed to clarify these differences and investigate the actual care provided to elderly patients with pneumonia in nursing hospitals. METHODS: Multicenter questionnaire surveys of 179 patients admitted to nursing homes and long-term care beds in hospitals of three healthcare corporations, their families, and their physicians were conducted between January and August 2018. The questionnaires mainly assessed preferences for life-prolonging medical care procedures, including antibiotic treatments, in terminal-phase pneumonia. A follow-up survey regarding the prognosis and the actual care provided by the physicians was conducted 1 year after the first survey. RESULTS: Only 16.2% of the patients had sufficient prior discussions with their families about their care. More families preferred cardiac massage, intubation, and tracheostomy, while fewer families preferred peripheral intravenous fluids or antibiotics than physicians. A total of 30 patients' families (16.7%) answered to withhold antibiotic treatment, while all physicians supported antibiotic administration. The only significant factor related to withholding antibiotics was high age (P = 0.0057). The follow-up survey administered to the doctors revealed that 49 patients (35.7%) had died within one year. Of the 137 patients, 54 patients (39.4%) had developed pneumonia during this observation period and all were treated with antibiotics. CONCLUSIONS: This study revealed large discrepancies between patients/families and physicians regarding preferences for care. Medical staff should make efforts to fill the gap by ensuring advance care planning.

17.
AIDS Res Ther ; 17(1): 38, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32646446

RESUMO

BACKGROUND: Vacuolar encephalomyelopathy, a disregarded diagnosis lately, was a major neurological disease in the terminal stages of human immunodeficiency virus (HIV)-1 infection in the pre-antiretroviral therapy (ART) era. Granulomatous-lymphocytic interstitial lung disease (GLILD) was classically identified as a non-infectious complication of common variable immunodeficiency; however, it is now being recognized in other immunodeficiency disorders. Here, we report the first case of GLILD accompanied by vacuolar encephalomyelopathy in a newly diagnosed HIV-infected man. CASE PRESENTATION: A 40-year-old Japanese man presented with chronic dry cough and progressing paraplegia. Radiological examination revealed diffuse pulmonary abnormalities in bilateral lungs, focal demyelinating lesions of the spinal cord, and white matter lesions in the brain. He was diagnosed with GLILD based on marked lymphocytosis detecting in bronchoalveolar lavage, and transbronchial-biopsy proven T-cellular interstitial lung disease with granulomas. Microbiological examinations did not reveal an etiologic agent. The patient was also diagnosed with HIV-associated vacuolar encephalomyelopathy on the basis of an elevated HIV viral load in cerebrospinal fluid. After initiating ART, the brain lesions and paraplegia improved significantly, and interstitial abnormalities of the lungs and cough disappeared. CONCLUSION: This report highlights that even in the post-ART era in developed countries with advanced healthcare services, HIV-associated vacuolar encephalomyelopathy should be considered in the differential diagnosis of a progressive neurological disorder during the first visit. Furthermore, GLILD may represent an HIV-associated pulmonary manifestation that can be treated by ART.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , HIV/efeitos dos fármacos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças por Armazenamento dos Lisossomos/virologia , Doenças Musculares/virologia , Adulto , Diagnóstico Diferencial , HIV/patogenicidade , Infecções por HIV/diagnóstico , Humanos , Pulmão/patologia , Doenças Pulmonares Intersticiais/virologia , Masculino , Vacúolos/patologia
18.
Sci Rep ; 10(1): 9789, 2020 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-32555245

RESUMO

Elm1 is a serine/threonine kinase involved in multiple cellular functions, including cytokinesis, morphogenesis, and drug resistance in Saccharomyces cerevisiae; however, its roles in pathogenic fungi have not been reported. In this study, we created ELM1-deletion, ELM1-reconstituted, ELM1-overexpression, and ELM1-kinase-dead strains in the clinically important fungal pathogen Candida glabrata and investigated the roles of Elm1 in cell morphology, stress response, and virulence. The elm1Δ strain showed elongated morphology and a thicker cell wall, with analyses of cell-wall components revealing that this strain exhibited significantly increased chitin content relative to that in the wild-type and ELM1-overexpression strains. Although the elm1Δ strain exhibited slower growth than the other two strains, as well as increased sensitivity to high temperature and cell-wall-damaging agents, it showed increased virulence in a Galleria mellonella-infection model. Moreover, loss of Elm1 resulted in increased adhesion to agar plates and epithelial cells, which represent important virulence factors in C. glabrata. Furthermore, RNA sequencing revealed that expression levels of 30 adhesion-like genes were elevated in the elm1Δ strain. Importantly, all these functions were mediated by the kinase activity of Elm1. To our knowledge, this is the first report describing the functional characterization of Elm1 in pathogenic fungi.


Assuntos
Candida glabrata/enzimologia , Proteínas Fúngicas/fisiologia , Proteínas Quinases/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Animais , Antifúngicos/farmacologia , Candida glabrata/efeitos dos fármacos , Candida glabrata/patogenicidade , Candida glabrata/ultraestrutura , Candidíase/microbiologia , Adesão Celular , Linhagem Celular , Proliferação de Células , Parede Celular/genética , Parede Celular/fisiologia , Proteínas Fúngicas/genética , Perfilação da Expressão Gênica , Regulação Fúngica da Expressão Gênica , Camundongos , Testes de Sensibilidade Microbiana , Mutagênese , Fenótipo , Proteínas Quinases/genética , RNA-Seq , Proteínas de Saccharomyces cerevisiae/genética , Estresse Fisiológico , Virulência
19.
BMC Infect Dis ; 20(1): 281, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32295538

RESUMO

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that commonly has a lethal course caused by the tick-borne Huaiyangshan banyang virus [former SFTS virus (SFTSV)]. The viral load in various body fluids in SFTS patients and the best infection control measure for SFTS patients have not been fully established. CASE PRESENTATION: A 79-year-old man was bitten by a tick while working in the bamboo grove in Nagasaki Prefecture in the southwest part of Japan. Due to the occurrence of impaired consciousness, he was referred to Nagasaki University Hospital for treatment. The serum sample tested positive for SFTSV-RNA in the genome amplification assay, and he was diagnosed with SFTS. Furthermore, SFTSV-RNA was detected from the tick that had bitten the patient. He was treated with multimodal therapy, including platelet transfusion, antimicrobials, antifungals, steroids, and continuous hemodiafiltration. His respiration was assisted with mechanical ventilation. On day 5, taking the day on which he was hospitalized as day 0, serum SFTSV-RNA levels reached a peak and then decreased. However, the cerebrospinal fluid collected on day 13 was positive for SFTSV-RNA. In addition, although serum SFTSV-RNA levels decreased below the detectable level on day 16, he was diagnosed with pneumonia with computed tomography. SFTSV-RNA was detected in the bronchoalveolar lavage fluid on day 21. By day 31, he recovered consciousness completely. The pneumonia improved by day 51, but SFTSV-RNA in the sputum remained positive for approximately 4 months after disease onset. Strict countermeasures against droplet/contact infection were continuously conducted. CONCLUSIONS: Even when SFTSV genome levels become undetectable in the serum of SFTS patients in the convalescent phase, the virus genome remains in body fluids and tissues. It may be possible that body fluids such as respiratory excretions become a source of infection to others; thus, careful infection control management is needed.


Assuntos
Líquidos Corporais/virologia , Encefalopatias/virologia , Infecções por Bunyaviridae/epidemiologia , Hemorragia Gastrointestinal/virologia , Phlebovirus/genética , Pneumonia/virologia , RNA Viral/sangue , Idoso , Animais , Encefalopatias/tratamento farmacológico , Líquido da Lavagem Broncoalveolar/virologia , Infecções por Bunyaviridae/tratamento farmacológico , Infecções por Bunyaviridae/virologia , Terapia Combinada , Hemorragia Gastrointestinal/tratamento farmacológico , Hospitais Universitários , Humanos , Japão/epidemiologia , Masculino , Técnicas de Amplificação de Ácido Nucleico , Phlebovirus/isolamento & purificação , Pneumonia/tratamento farmacológico , Escarro/virologia , Carrapatos/virologia , Resultado do Tratamento , Carga Viral
20.
Sci Rep ; 10(1): 3814, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32123235

RESUMO

Gastrointestinal colonization has been considered as the primary source of candidaemia; however, few established mouse models are available that mimic this infection route. We therefore developed a reproducible mouse model of invasive candidiasis initiated by fungal translocation and compared the virulence of six major pathogenic Candida species. The mice were fed a low-protein diet and then inoculated intragastrically with Candida cells. Oral antibiotics and cyclophosphamide were then administered to facilitate colonization and subsequent dissemination of Candida cells. Mice infected with Candida albicans and Candida tropicalis exhibited higher mortality than mice infected with the other four species. Among the less virulent species, stool titres of Candida glabrata and Candida parapsilosis were higher than those of Candida krusei and Candida guilliermondii. The fungal burdens of C. parapsilosis and C. krusei in the livers and kidneys were significantly greater than those of C. guilliermondii. Histopathologically, C. albicans demonstrated the highest pathogenicity to invade into gut mucosa and liver tissues causing marked necrosis. Overall, this model allowed analysis of the virulence traits of Candida strains in individual mice including colonization in the gut, penetration into intestinal mucosa, invasion into blood vessels, and the subsequent dissemination leading to lethal infections.


Assuntos
Candida/patogenicidade , Candidíase/microbiologia , Animais , Candidíase/patologia , Modelos Animais de Doenças , Intestinos/microbiologia , Camundongos , Virulência
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