RESUMO
We definitively characterized Mycobacterium angelicum, an aquatic zoonotic opportunistic pathogen of the M. szulgai complex, using a polyphasic approach that included whole-genome sequencing. The sequence was obtained on the island of Tahiti, French Polynesia, from a urine specimen collected from a patient experiencing a urinary tract infection.
Assuntos
Infecções por Mycobacterium não Tuberculosas , Mycobacterium , Sistema Urinário , Humanos , Mycobacterium/genética , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Polinésia/epidemiologiaRESUMO
BACKGROUND & AIMS: Hepatitis E virus (HEV) infection can evolve to chronic hepatitis in immunocompromised patients. Pegylated α-interferon can effectively treat chronic HEV infection after liver transplantation but is contraindicated for kidney transplantation. We assessed the antiviral effect of ribavirin monotherapy in patients with chronic HEV infection following kidney transplantation. METHODS: In a pilot study performed at Toulouse University Hospital, 6 patients that received kidney transplants who were positive for HEV RNA (infected with HEV for 36.5 months; [range, 11-46 months]) were given ribavirin monotherapy for 3 months. Ribavirin was given at 600-800 mg/day in 2 separate doses, based on the patient's ability to clear creatinine. RESULTS: Median serum concentration of HEV RNA at baseline was 5.77 log copies/mL (range, 4.35-7.35 log copies/mL). Three months after ribavirin therapy commenced, HEV RNA was undetectable in serum samples from all patients. A sustained virologic response was observed in 4 patients; the other 2 patients relapsed at 1 and 2 months after ribavirin therapy ended. At the end of the study, all patients had normal levels of alanine and aspartate aminotransferase. Anemia was the main side effect caused by ribavirin therapy. CONCLUSIONS: Ribavirin monotherapy inhibits the replication of HEV in vivo and might induce a sustained virological response in patients with chronic HEV infections. Further studies are required to determine the optimal duration of ribavirin therapy.
Assuntos
Antivirais/uso terapêutico , Vírus da Hepatite E/fisiologia , Hepatite E/tratamento farmacológico , Transplante de Rim/efeitos adversos , Ribavirina/uso terapêutico , Replicação Viral/efeitos dos fármacos , Idoso , Antivirais/administração & dosagem , Doença Crônica , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Anticorpos Anti-Hepatite/análise , Hepatite E/transmissão , Hepatite E/virologia , Vírus da Hepatite E/efeitos dos fármacos , Humanos , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , RNA Viral/análise , Estudos Retrospectivos , Ribavirina/administração & dosagem , Resultado do TratamentoRESUMO
OBJECTIVE: Human cytomegalovirus can be reactivated after orthotopic liver transplantation in patients who are seropositive for cytomegalovirus. Whether those cytomegalovirus-seropositive patients require immediate posttransplant (anti)- cytomegalovirus prophylactic therapy or preemptive treatment as opposed to deferred treatment remains controversial. The aims of our study were to evaluate the relevance of cytomegalovirus monitoring with quantitative real-time polymerase chain reaction in whole blood and to analyze the factors that determine the treatment of the first episode of cytomegalovirus infection with intravenous ganciclovir in seropositive liver-transplant patients. PATIENTS AND METHODS: Forty-two cytomegalovirus-seropositive liver-transplant patients were assessed for cytomegalovirus DNAemia every 2 weeks until posttransplant day 90 and every 3 to 4 weeks until day 180. Biochemical and hematologic parameters were also prospectively monitored. RESULTS: Cytomegalovirus DNAemia was detected at least once in 27 patients (64%). Treatment was initiated in 12 patients (group 1) but not in 15 others (group 2). Median HCMV viral loads of the first positive and the highest DNAemia were statistically higher in group 1 than in group 2 (P = 0.01). Univariate analysis of DNAemia showed that alkaline phosphatase levels were significantly higher in group 1 than in group 2 (P = .0011) and that hemoglobin levels were significantly lower in group 1 than in group 2 (P = .0443). The results of multivariate analysis showed that the only factor that predicted the treatment of the first episode of HCMV DNAemia was a level of alkaline phosphatase greater than 150 IU/L [odds ratio, 20; range, 1.97-203.32; P = .01]. CONCLUSIONS: A combination of criteria, including viral-load kinetics, clinical factors, alkaline phosphatase levels (in particular), and the patient's immune condition, is required to efficiently monitor patients who are seropositive for cytomegalovirus after orthotopic liver transplantation.
Assuntos
Infecções por Citomegalovirus/epidemiologia , Citomegalovirus/genética , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/virologia , Creatinina/sangue , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/diagnóstico , Monitoramento Ambiental/métodos , Monitoramento Epidemiológico , Rejeição de Enxerto/epidemiologia , Humanos , Reação em Cadeia da Polimerase/métodos , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: Type II or III cryoglobulins are fairly prevalent in renal-transplant (RT) patients, and are often related to chronic hepatitis C virus (HCV) infection. However, they rarely result in graft dysfunction. They are sustained by proliferation of oligoclonal B-cells. Systemic B-cell depletion and clinical remission of the systemic effects of cryoglobulins have been achieved in HCV-positive immunocompetent patients with a human/mouse chimeric monoclonal antibody that specifically reacts with the CD20 antigen (i.e., rituximab). Thus, this provides the rationale to use rituximab for cryoglobulin-related graft dysfunction in RT patients. METHODS: Three RT patients, of whom one was HCV-positive, developed renal-function impairment long after transplantation, as well as de novo nephrotic syndrome (n=2) and severe hypertension (n=2). This latter case was related to type III cryoglobulinemia and was associated with membranoproliferative glomerulonephritis. In addition to their baseline standard immunosuppression, the patients were given weekly rituximab infusions of 375 mg/m (two infusions in patient and four infusions for the other two cases). RESULTS: This treatment resulted in a dramatic improvement in renal parameters, particularly in a sustained remittence of nephrotic syndrome, a sustained clearance of cryoglobulins in two cases, but also in severe infectious complications in two cases. CONCLUSION: We conclude that rituximab therapy is highly effective in cryoglobulin-related renal dysfunction in RT patients; however, due to chronic immunosuppression, this is at the expense of infectious complications.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Crioglobulinemia/tratamento farmacológico , Transplante de Rim/patologia , Anticorpos Monoclonais Murinos , Biópsia , Quimioterapia Combinada , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Testes de Função Renal , Transplante de Rim/imunologia , Transplante de Rim/fisiologia , Pessoa de Meia-Idade , RituximabAssuntos
Vírus BK/isolamento & purificação , Transplante de Rim , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/terapia , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/terapia , Humanos , Linfo-Histiocitose Hemofagocítica/virologia , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Tenofovir therapy has been found to be efficient in treating hepatitis B virus (HBV) in nontransplant patients. However, in the setting of solid-organ transplantation, the efficacy of tenofovir has not been tested. The aim of this pilot study was to assess the clinical and biologic response and tolerance to tenofovir therapy in HBV-positive organ transplant recipients. METHODS: Seven patients, three kidney, three liver, and one cardiac transplant recipients, with chronic HBV infection were partial responders to adefovir (n=7), lamivudine (n=7), or entecavir (n=5) therapy. Consequently, they were placed on tenofovir therapy (245 mg daily, which was adapted to renal function) alone (n=4) or in combination with lamivudine (n=3). Tenofovir therapy was assessed at 1, 3, 6, and 12 months postinitiation or at the last follow-up. RESULTS: HBV DNA viral load (4.16 [2.03-5.56] log10 copies/mL at baseline) became significantly decreased to 3.15 (1.08-5.17), 2.88 (1.3-4.3), 3.53 (1.3-5.75), 3.33 (1.3-7.57), and 2.31 (1.3-4.81) log copies/mL at 1, 3, 6, and 12 months posttenofovir initiation and at last follow-up, respectively (P=0.02). Three patients were HBV DNA negative at the last follow-up. Liver enzyme levels did not change significantly throughout the follow-up period. Clinical and biologic tolerance was excellent. CONCLUSIONS: Even though HBV DNA clearance was not achieved in all patients, the results of this pilot study are encouraging and demonstrate that tenofovir therapy is safe and efficacious in treating HBV-positive organ transplant patients. However, a larger trial is needed to confirm these preliminary results.