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1.
Rinsho Ketsueki ; 60(9): 1337-1340, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31597861

RESUMO

Various types of infectious complications could develop after allogeneic hematopoietic stem cell transplantation (HSCT) due to the associated intensive immunosuppression. Cellular immunity is also impaired, resulting in a higher incidence of viral infections when compared with standard chemotherapy. Cytomegalovirus (CMV) reactivates in seropositive patients under immunosuppression after allogeneic HSCT, causing complications, such as pneumonitis, gastroenteritis, and retinitis. Because intervention before the onset of disease, rather than after, can improve prognosis, preemptive therapy guided by early detection of CMV reactivation has been extensively used. Recently, the introduction of a less myelotoxic agent, letermovir, has enabled prophylactic therapy to be administered safely and effectively. In addition, prophylactic letermovir is expected to reduce transplant-related mortality. However, the onset of CMV infection/disease as either a breakthrough infection or after the discontinuation of letermovir is still problematic. In this section, the management tips for CMV infection after allogeneic HSCT have been summarized.


Assuntos
Acetatos/uso terapêutico , Antivirais/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Quinazolinas/uso terapêutico , Citomegalovirus , Infecções por Citomegalovirus/etiologia , Humanos , Incidência
2.
Expert Opin Drug Saf ; 18(11): 1017-1030, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31478398

RESUMO

Introduction: Human cytomegalovirus (HCMV) is a major contributor of morbidity and mortality, and its management is essential for the successful outcome of solid organ and hematopoietic stem cell transplantation. Areas covered: This review discusses the safety profiles of currently available and emerging antiviral drugs and the other strategies for HCMV prevention and treatment after transplantation. Expert opinion: Strategies for management of HCMV rely largely on the use of antiviral agents that inhibit viral DNA polymerase (ganciclovir/valganciclovir, foscarnet, and cidofovir/brincidofovir) and viral terminase complex (letermovir), with different types and degrees of adverse effects. An investigational agent, maribavir, exerts its anti-CMV effect through UL97 inhibition, and its safety profile is under clinical evaluation. In choosing the antiviral medication to use, it is important to consider these safety profiles in addition to overall efficacy. In addition to antiviral drugs, reduction of immunosuppression is often generally needed in the management of HCMV infection, but with a potential risk of allograft rejection or graft-versus-host disease. The use of HCMV-specific or non-specific intravenous immunoglobulins remains debated, while adoptive HCMV-specific T cell therapy remains investigational, and associated with unique set of adverse effects.


Assuntos
Antivirais/administração & dosagem , Infecções por Citomegalovirus/prevenção & controle , Infecções Oportunistas/prevenção & controle , Antivirais/efeitos adversos , Infecções por Citomegalovirus/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunossupressores/administração & dosagem , Infecções Oportunistas/virologia , Transplante de Órgãos/efeitos adversos , Transplante de Órgãos/métodos
3.
Ann Transplant ; 24: 412-417, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31296835

RESUMO

BACKGROUND Cytomegalovirus (CMV) and BK virus (BKV) are post-transplant opportunistic viral infections that affect patient and graft survival. This study was designed to evaluate the risk of BKV nephropathy and CMV disease in kidney transplant recipients who received induction therapy with ATG or basiliximab. MATERIAL AND METHODS We retrospectively analyzed information on 257 adult patients who underwent kidney transplantation between January 2007 and 2017. Patients were categorized into 3 groups according to the induction therapies. The primary endpoint was the onset of CMV disease or biopsy-confirmed BKV nephropathy. The secondary endpoints were biopsy-proven rejection episodes, graft loss, loss to follow-up, and death. RESULTS We followed 257 patients for a median of 55.5 months. The incidence of CMV disease was significantly higher in the only ATG group compared to the group without induction treatment (p<0.001). There was no significant difference in the incidence of BKV nephropathy among groups (p>0.05). The dosage of ATG (OR, 10.685; 95% CI, 1.343 5 to 85.009; P=0.025) was independent risk factor for death. CONCLUSIONS This study demonstrated that a higher dosage of ATG in high-risk patients is associated with an increased risk of CMV disease and patient death, also, reducing the dosage may be a rational strategy for increasing graft and patient's survival.


Assuntos
Infecções por Citomegalovirus/etiologia , Imunossupressores/efeitos adversos , Quimioterapia de Indução/efeitos adversos , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/etiologia , Infecções Tumorais por Vírus/etiologia , Adulto , Vírus BK , Citomegalovirus , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
4.
Ann Hematol ; 98(9): 2197-2211, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31321454

RESUMO

Incidence and outcome of microbiologically documented bacterial/viral infections and invasive fungal disease (IFD) in children and adults after hematopoietic cell transplantation (HCT) were compared in 650 children and 3200 adults in multicenter cross-sectional nationwide study. Infections were diagnosed in 60.8% children and 35.0% adults, including respectively 69.1% and 63.5% allo-HCT, and 33.1% and 20.8% auto-HCT patients. The incidence of bacterial infections was higher in children (36.0% vs 27.6%; p < 0.0001). Infections with Gram-negative bacteria were more frequent than Gram-positives in adults (64.6% vs 44.8%; p < 0.0001). Outcome of bacterial infections was better in children (95.5% vs 91.4%; p = 0.0011). The IFD incidence (25.3% vs 6.3%; p < 0.0001) and outcome (88.0% vs 74.9%; p < 0.0001) were higher in children. The incidence of viral infections was higher in children after allo-HCT (56.3% vs 29.3%; p < 0.0001), and auto-HCT (6.6% vs 0.8%; p < 0.0001). Outcome of viral infections was better in children (98.6% vs 92.3%; p = 0.0096). Infection-related mortality was 7.8% in children and 18.4% in adults (p < 0.0001). No child after auto-HCT died of infection. Adult age, mismatched transplants, acute leukemia, chronic GVHD, CMV reactivation, infection with Gram-negatives, and duration of infection > 21 days were risk factors for death from infection. In conclusion, pediatric patients have 2.9-fold higher incidence and 2.5-fold better outcome of infections than adults after HCT.


Assuntos
Infecções Bacterianas/epidemiologia , Infecções por Citomegalovirus/epidemiologia , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas , Infecções Fúngicas Invasivas/epidemiologia , Doença Aguda , Adolescente , Adulto , Fatores Etários , Idoso , Infecções Bacterianas/etiologia , Criança , Pré-Escolar , Doença Crônica , Estudos Transversais , Infecções por Citomegalovirus/etiologia , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Incidência , Lactente , Recém-Nascido , Infecções Fúngicas Invasivas/etiologia , Leucemia , Masculino , Pessoa de Meia-Idade , Fatores de Risco
5.
Rinsho Ketsueki ; 60(6): 635-645, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31281156

RESUMO

In patients who undergo hematopoietic stem cell transplantation (HSCT), cytomegalovirus (CMV) infection directly or indirectly increases all-cause and non-relapse mortality rates. Although preemptive therapy suppresses CMV infection, it does not improve non-relapse mortality rates in patients with CMV reactivation compared to patients with no CMV reactivation. According to the World Health Organization International Standards (WHO IS), quantitative polymerase chain reaction has been recently adopted as the global standard for monitoring CMV, and maribavir, brincidofovir, and letermovir have been developed as new antiviral drugs for the treatment of CMV infection. Letermovir, a first-class anti-CMV agent, strongly inhibits the CMV DNA terminase complex, which is required for viral DNA cleavage and packaging. It significantly suppressed CMV infection in a phase III clinical trial, thereby improving the overall survival of patients who undergo HSCT. Vaccines and cell therapies for CMV must be further developed.


Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Citomegalovirus , Infecções por Citomegalovirus/etiologia , Humanos , Transplante Homólogo
6.
Transplant Proc ; 51(6): 1810-1815, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31256873

RESUMO

BACKGROUND: Cytomegalovirus infection (CMV) after kidney transplantation leads to increased morbidity and mortality. Whether the cause of end-stage renal disease (ESRD) influences the risk of CMV infection post-transplant is not known. METHODS: We analyzed data from 2741 adult kidney transplant recipients from January 1993 through December 2014. The causes of ESRD included diabetes mellitus (n = 947), hypertension (n = 442), polycystic kidney disease (n = 549), and glomerulonephritis (GN) (n = 803). The primary outcome was incidence of CMV infection, defined as the first episode of detectable CMV DNA in the blood following transplant. RESULTS: Three hundred and thirty patients developed a CMV infection over a median follow-up of 4.5 years. Patients with diabetes mellitus (DM) as the cause of ESRD had a higher incidence of CMV infection post-transplant compared to patients with GN (2.37 vs 1.58/100 person-years, P < .005) whereas hypertension (HTN) and autosomal dominant polycystic kidney disease (PKD) were similar (2.17 and 2.07/100 person-years). DM was associated with a 35% higher risk of CMV infection compared to GN in unadjusted analyses [hazard ratio=1.35 [95% confidence interval 1.02-1.78], P = .04). However, after adjustment for age, the risk of CMV infection was similar in all groups (DM: age-adjusted hazard ratio 1.02 [0.78-1.39]; HTN: 0.96 (0.67-1.36); PKD: 1.08 [0.78-1.48]; compared to GN). The risk of CMV infection increased with age (adjusted hazard ratio=1.32 [1.18-1.47] for every decade of life, P < .001). CONCLUSIONS: Our study demonstrates that the cause of ESRD is not a significant risk factor for CMV infection in kidney transplant recipients once adjusted for age. Future studies are needed to identify risk factors for CMV infection to define patient-centered monitoring and prevention.


Assuntos
Infecções por Citomegalovirus/epidemiologia , Nefropatias/epidemiologia , Falência Renal Crônica/etiologia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias , Adulto , Antivirais/uso terapêutico , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/virologia , Feminino , Humanos , Incidência , Nefropatias/virologia , Falência Renal Crônica/cirurgia , Falência Renal Crônica/virologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco
7.
PLoS Pathog ; 15(7): e1007914, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31356650

RESUMO

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that can cause disability in newborns and serious clinical diseases in immunocompromised patients. HCMV has a large genome with enormous coding potential; its viral particles are equipped with complicated glycoprotein complexes and can infect a wide range of human cells. Although multiple host cellular receptors interacting with viral glycoproteins have been reported, the mechanism of HCMV infection remains a mystery. Here we report identification of adipocyte plasma membrane-associated protein (APMAP) as a novel modulator active in the early stage of HCMV infection. APMAP is necessary for HCMV infection in both epithelial cells and fibroblasts; knockdown of APMAP expression significantly reduced HCMV infection of these cells. Interestingly, ectopic expression of human APMAP in cells refractory to HCMV infection, such as canine MDCK and murine NIH/3T3 cells, promoted HCMV infection. Furthermore, reduction in viral immediate early (IE) gene transcription at 6 h post infection and delayed nucleus translocation of tegument delivered pp65 at 4 h post infection were detected in APMAP-deficient cells but not in the wildtype cells. These results suggest that APMAP plays a role in the early stage of HCMV infection. Results from biochemical studies of APMAP and HCMV proteins suggest that APMAP could participate in HCMV infection through interaction with gH/gL containing glycoprotein complexes at low pH and mediate nucleus translocation of tegument pp65. Taken together, our results suggest that APMAP functions as a modulator promoting HCMV infection in multiple cell types and is an important player in the complex HCMV infection mechanism.


Assuntos
Infecções por Citomegalovirus/metabolismo , Infecções por Citomegalovirus/virologia , Citomegalovirus/patogenicidade , Glicoproteínas de Membrana/metabolismo , Adipócitos/metabolismo , Adipócitos/virologia , Animais , Membrana Celular/metabolismo , Membrana Celular/virologia , Citomegalovirus/genética , Citomegalovirus/metabolismo , Infecções por Citomegalovirus/etiologia , Cães , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Fibroblastos/metabolismo , Fibroblastos/virologia , Técnicas de Inativação de Genes , Interações entre Hospedeiro e Microrganismos , Humanos , Células Madin Darby de Rim Canino , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/genética , Camundongos , Células NIH 3T3 , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Estruturais Virais/metabolismo , Virulência , Internalização do Vírus
8.
Int J Mol Sci ; 20(11)2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31151230

RESUMO

Cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation (HSCT) is one of the critical infectious complications related to host immune recovery. The spectrum of CMV infection is quite extensive, from asymptomatic CMV reactivation presenting mainly as CMV DNAemia to fatal CMV diseases involving gut, liver, lungs, or brain. In addition to organ involvement, CMV reactivation can exert indirect effects such as immunosuppression or graft failure that may result in the development of concurrent infectious complications. Currently, preemptive therapy, which is based on PCR-based monitoring of CMV from blood, is a mainstay enabling improvement in CMV-related outcomes. During the past decades, new antiviral drugs, clinical trials for prophylaxis in high-risk groups, and vaccines for preventing CMV infection have been introduced. In addition, data for immunologic monitoring and adoptive immunotherapy have also been accumulated. Here, we review the current status and recent updates in this field, with future perspectives including immunotherapy in HSCT recipients.


Assuntos
Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Antivirais/uso terapêutico , Ensaios Clínicos como Assunto , Citomegalovirus/imunologia , Vacinas contra Citomegalovirus/administração & dosagem , Vacinas contra Citomegalovirus/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Hospedeiro Imunocomprometido , Imunogenicidade da Vacina , Imunoterapia , Vigilância em Saúde Pública , Padrão de Cuidado , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento
9.
Int J Hematol ; 110(1): 77-85, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31127456

RESUMO

This multicenter phase II study (UMIN000008145) aims to investigate the efficacy and safety of six cycles of combination therapy (RBD) comprising rituximab, bendamustine, and dexamethasone (DEX) for relapsed or refractory (RR) indolent B-cell non-Hodgkin lymphoma (B-NHL) and mantle cell lymphoma (MCL). Although the initial study protocol comprised 20 mg/body DEX on days 1 and 2, and 10 mg/body on days 3-5 [high-dose (HD-) DEX group], the dose of DEX was later decreased to 8 mg/body on days 1 and 2 [low-dose (LD-) DEX group] due to frequent cytomegalovirus (CMV) antigenemia and recurrent retinitis. We enrolled 33 patients, and LD-DEX and HD-DEX were administered in 15 and 18 patients, respectively. The overall response and the 3-year progression-free survival rates were 88% and 75.5%, respectively. The leading adverse event was myelosuppression. Incidence of grade 3-4 leukocytopenia, neutropenia, and lymphocytopenia was 55%, 67%, and 91%, respectively. The most frequent nonhematological adverse events were CMV antigenemia and rash (33% and 30%, respectively). Incidence of CMV antigenemia over 10/100,000 white blood cells was significantly lower with LD-DEX than that with HD-DEX (P = 0.0127). In conclusion, RBD showed significant effectiveness for RR indolent B-NHL and MCL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Linfoma de Célula do Manto/tratamento farmacológico , Terapia de Salvação/métodos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Bendamustina/administração & dosagem , Infecções por Citomegalovirus/etiologia , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Leucopenia/etiologia , Linfoma de Células B/complicações , Linfoma de Célula do Manto/complicações , Masculino , Pessoa de Meia-Idade , Neutropenia/etiologia , Rituximab/administração & dosagem , Terapia de Salvação/efeitos adversos , Adulto Jovem
10.
Infect Dis Clin North Am ; 33(2): 485-500, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30940460

RESUMO

Cytomegalovirus (CMV) may no longer be the menace that plagues stem cell transplant outcomes, owing to marked improvements in transplantation techniques and methods of prophylaxis. However, it still remains a common and morbid problem for recipients of stem cell transplant and patients with certain hematologic malignancies. This article discusses the epidemiology and risk factors of CMV infection and disease, associated morbidity and mortality, diagnosis, and clinical features of clinical syndromes associated with CMV and the principles of management of CMV, with special attention to resistant CMV as it pertains to infectious disease specialists.


Assuntos
Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/fisiopatologia , Farmacorresistência Viral Múltipla , Neoplasias Hematológicas/virologia , Transplante de Células-Tronco/efeitos adversos , Antivirais/uso terapêutico , Citomegalovirus/efeitos dos fármacos , Infecções por Citomegalovirus/mortalidade , Gerenciamento Clínico , Ganciclovir/uso terapêutico , Neoplasias Hematológicas/complicações , Humanos , Fatores de Risco
11.
Ann Hematol ; 98(8): 1999-2001, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30824957
12.
Mayo Clin Proc ; 94(1): 166-170, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30611443

RESUMO

The optimal approach to preventing cytomegalovirus (CMV) disease after face transplant is unknown. We report an individualized hybrid approach, initially using valganciclovir prophylaxis followed by surveillance and preemptive therapy guided by viral and immunologic markers. A 31-year-old man received a near-total face allotransplant for gunshot injury-related severe facial deformities. He was CMV seronegative, and the donor was CMV seropositive (D+/R- mismatch), and he received intravenous ganciclovir followed by oral valganciclovir prophylaxis. Monthly CD8+ T-cell immune competence assay revealed no CMV-specific CD8+ T-cell immunity development during valganciclovir prophylaxis. Because of severe leukopenia, valganciclovir was discontinued at 7 months after transplant when the patient had recovered and sustained normal global CD8+ T-cell function. Weekly CMV polymerase chain reaction testing detected asymptomatic CMV replication (plasma CMV, 549 IU/mL) 3 months later. Short-course preemptive valganciclovir treatment resulted in sustained virologic clearance. The patient had development of CMV-specific CD8+ T cells (12 cells/µL) together with CMV IgM and IgG. No rejection or infection relapse was detected 20 months after transplant. In conclusion, viral and immunologic monitoring allowed for an individualized approach to effective CMV disease prevention after face transplant. This case highlights the importance of understanding the interplay between the host immunity and the pathogen in determining the clinical course and outcome of CMV and other infectious disease syndromes.


Assuntos
Antibioticoprofilaxia/métodos , Infecções por Citomegalovirus/prevenção & controle , Citomegalovirus , Transplante de Face/efeitos adversos , Ganciclovir/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Adulto , Antivirais/uso terapêutico , Infecções por Citomegalovirus/etiologia , Rejeição de Enxerto/etiologia , Humanos , Masculino
13.
Ann Hematol ; 98(4): 1009-1020, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30666434

RESUMO

Cytomegalovirus (CMV) infection and primary disease relapse remain challenging problems after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We sought to assess the association between CMV infection and disease relapse after transplantation. PubMed, EMBASE, the Cochrane Library, SCI, and Chinese Biomedicine Databases were searched up to July 1, 2018, for all studies that investigate pre-transplant CMV serostatus, CMV replication, and primary disease relapse in allo-HSCT patients with hematologic malignancies. Meta-analysis of 24 eligible cohort studies showed a significantly lower relapse risk after allo-HSCT in patients with CMV replication in acute myeloid leukemia (AML) (HR = 0.64, 95% CI, 0.50-0.83; P < 0.001) subgroup. However, CMV replication was associated with increased non-relapse mortality (NRM) in AML patients (HR = 1.64, 95% CI, 1.46-1.85; P < 0.001), but not associated with overall survival (OS) or graft-versus-host disease for AML patients (P > 0.05). There was no association between pre-transplant CMV serostatus and disease relapse, although D-/R- was associated with better OS in acute leukemia patients (HR = 0.89, 95% CI, 0.83-0.96; P = 0.003). In AML patients, CMV replication may be a protective predictor against disease relapse, although the potential benefit of CMV replication is offset by increased NRM.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Leucemia Mieloide Aguda , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/mortalidade , Infecções por Citomegalovirus/terapia , Intervalo Livre de Doença , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Estudos Observacionais como Assunto , Recidiva , Fatores de Risco , Taxa de Sobrevida
14.
BMC Infect Dis ; 19(1): 70, 2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30658589

RESUMO

BACKGROUND: Visceral leishmaniasis (VL) is becoming endemic in São Paulo state, in the southeastern region of Brazil. Unusual manifestations with non-specific signs and symptoms may make diagnosis difficult and delay treatment, increasing the risk of severity and death, particularly in new endemic areas. There are few studies on patients with these characteristics in Brazil. We describe a case series of unusual manifestations of VL in children and its spatial dispersion in the western region of São Paulo state. CASES PRESENTATION: From 2009 to 2014, five clinical cases involving children treated in the Regional Hospital of Presidente Prudente (RH) were selected. Two patients had multiple relapses requiring liposomal amphotericin B; one patient had VL-cytomegalovirus-dengue co-infection and liver injury; one patient was diagnosed with X-linked agammaglobulinemia, a primary immunodeficiency; and one patient was diagnosed with VL-human immunodeficiency virus/acquired immunodeficiency syndrome (VL-HIV/AIDS) co-infection. Primary or secondary immunodeficiencies were found in four children, and associated viral infections were found in three children. Three patients were referred from other hospitals to RH. With regard to the geographic spread of VL, more cases were found in the northern area, in the epicenter of the infection where the first cases were registered, flowing south; a spatial-temporal occurrence was found. CONCLUSIONS: Primary and secondary immunodeficiencies and viral co-infectious should be considered among unusual manifestations of VL, especially in those with multiple relapses. Spatial-temporal occurrence was found. Thus, integrated actions and effective monitoring of the disease are needed to complement curative practices to stem the tide of the epidemic.


Assuntos
Síndromes de Imunodeficiência/etiologia , Leishmaniose Visceral/etiologia , Síndrome de Imunodeficiência Adquirida/etiologia , Agamaglobulinemia/etiologia , Anfotericina B/uso terapêutico , Animais , Antiprotozoários/uso terapêutico , Brasil/epidemiologia , Criança , Pré-Escolar , Coinfecção/etiologia , Infecções por Citomegalovirus/etiologia , Cães , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/etiologia , Humanos , Lactente , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/epidemiologia , Masculino
15.
J Am Acad Dermatol ; 80(3): 670-678.e2, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30240780

RESUMO

BACKGROUND: The prognosis of drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is highly unpredictable. Severe complications, either related or unrelated to cytomegalovirus (CMV) reactivation, are a highly probable cause of death. OBJECTIVES: The aim was to establish a scoring system for DiHS/DRESS that can be used to monitor severity, predict prognosis, and stratify the risk of developing CMV disease and complications. METHODS: A retrospective analysis of 55 patients with DiHS/DRESS was performed. A composite score was created using clinical data. DiHS/DRESS patients were also stratified into 3 groups based on the scores to predict the risk of CMV reactivation and complications. RESULTS: This scoring system made it possible to predict CMV disease and complications. Scores ≥4 were associated with the later development of CMV disease and complications, while no patients with scores <4 developed complications. LIMITATIONS: This was a single-institution study with a relatively small patient cohort that lacked a validation cohort. CONCLUSIONS: Our scoring system may be useful for predicting CMV-related complications, and early intervention with anti-CMV agents should be considered in patients with scores ≥4 or with evidence of CMV reactivation.


Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/tratamento farmacológico , Síndrome de Hipersensibilidade a Medicamentos/complicações , Índice de Gravidade de Doença , Adolescente , Corticosteroides/uso terapêutico , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Antivirais/administração & dosagem , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/mortalidade , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Feminino , Ganciclovir/uso terapêutico , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Medição de Risco , Tempo para o Tratamento , Valganciclovir/uso terapêutico , Ativação Viral , Adulto Jovem
16.
Biol Blood Marrow Transplant ; 25(3): 577-586, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30342913

RESUMO

Human cytomegalovirus (CMV) infection and disease remains a significant cause of morbidity and mortality for hematopoietic cell transplantation (HCT) recipients. Disruption of or weak reconstitution of virus-specific cellular immune function, such as with certain HCT approaches, poses significant risk for CMV-related complications. The incidence of and risk factors for CMV infection and the nature of CMV disease were evaluated retrospectively among 356 consecutive HCT recipients transplanted at the National Institutes of Health using all graft sources, including bone marrow, peripheral blood stem cell (PBSC), and umbilical cord blood (UCB), and a range of in vivo and ex vivo approaches for graft-versus-host disease (GVHD) prophylaxis. The cumulative incidence of CMV infection was higher for CMV-seropositive recipients at 33%, regardless of donor CMV serostatus. Patients transplanted with CMV-seropositive donors had a significantly shorter duration of antiviral therapy. Among graft sources UCB was associated with the highest cumulative incidence of CMV infection at 65% and significantly longer treatment duration at a median of 36days, whereas PBSC HCT was associated with the lowest incidence at 26% and the shortest CMV treatment duration at a median of 21days. There were significant differences in the cumulative incidence of CMV infection by T cell manipulation strategy when systemic steroids were included as a risk-modifying event. Over one-third of CMV infections occurred in the setting of systemic steroid administration. CMV disease occurred in 5% of HCT recipients, with 70% of cases in the setting of treatment for GVHD. Although factors related to serostatus, graft source, and GVHD prophylaxis were associated with varied CMV infection incidence, unplanned post-HCT corticosteroid therapy contributed greatly to the incidence of both CMV infection and disease across HCT approaches, highlighting this post-HCT intervention as a key time to potentially tailor the approach to monitoring, preemptive therapy, and even prophylaxis.


Assuntos
Infecções por Citomegalovirus/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Adulto , Antivirais/uso terapêutico , Infecções por Citomegalovirus/etiologia , Feminino , Doença Enxerto-Hospedeiro/complicações , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , National Institutes of Health (U.S.) , Estudos Retrospectivos , Fatores de Risco , Esteroides/efeitos adversos , Doadores de Tecidos , Estados Unidos
17.
Mult Scler Relat Disord ; 27: 44-45, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30316174

RESUMO

Alemtuzumab (a drug highly active in multiple sclerosis) is a humanized monoclonal antibody targeting the surface molecule CD52. It causes a rapid depletion of innate and adaptive immune cells with a peak during the first month after infusion. Infection rates in alemtuzumab-treated patients with multiple sclerosis in clinical trials were higher in than in interferon beta-treated patients. Cytomegalovirus (CMV) primary infections and reactivations have been reported in this setting of patients. We describe the case of a patient that developed both viral (CMV) and bacterial pneumonia one month after alemtuzumab infusion for multiple sclerosis. Physicians dealing with this drug should be aware of this serious but treatable complication.


Assuntos
Alemtuzumab/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Infecções por Citomegalovirus/etiologia , Esclerose Múltipla/tratamento farmacológico , Pneumonia Bacteriana/etiologia , Pneumonia Viral/etiologia , Infecções por Citomegalovirus/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/imunologia , Pneumonia Viral/imunologia
18.
Biol Blood Marrow Transplant ; 25(2): 369-381, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30292744

RESUMO

Cytomegalovirus (CMV) infection is a common complication of allogeneic hematopoietic cell transplantation (HCT). In this trial, we randomized adult CMV-seropositive HCT recipients without CMV viremia at screening 2:1 to receive brincidofovir or placebo until week 14 post-HCT. Randomization was stratified by center and risk of CMV infection. Patients were assessed weekly through week 15 and every third week thereafter through week 24 post-HCT. Patients who developed clinically significant CMV infection (CS-CMVi; CMV viremia requiring preemptive therapy or CMV disease) discontinued the study drug and began anti-CMV treatment. The primary endpoint was the proportion of patients with CS-CMVi through week 24 post-HCT; patients who discontinued the trial or with missing data were imputed as primary endpoint events. Between August 2013 and June 2015, 452 patients were randomized at a median of 15 days after HCT and received study drug. The proportion of patients who developed CS-CMVi or were imputed as having a primary endpoint event through week 24 was similar between brincidofovir-treated patients and placebo recipients (155 of 303 [51.2%] versus 78 of 149 [52.3%]; odds ratio, .95 [95% confidence interval, .64 to 1.41]; P = .805); fewer brincidofovir recipients developed CMV viremia through week 14 compared with placebo recipients (41.6%; P < .001). Serious adverse events were more frequent among brincidofovir recipients (57.1% versus 37.6%), driven by acute graft-versus-host disease (32.3% versus 6.0%) and diarrhea (6.9% versus 2.7%). Week 24 all-cause mortality was 15.5% among brincidofovir recipients and 10.1% among placebo recipients. Brincidofovir did not reduce CS-CMVi by week 24 post-HCT and was associated with gastrointestinal toxicity.


Assuntos
Infecções por Citomegalovirus/prevenção & controle , Citomegalovirus , Citosina/análogos & derivados , Transplante de Células-Tronco Hematopoéticas , Organofosfonatos/administração & dosagem , Administração Oral , Adolescente , Adulto , Idoso , Aloenxertos , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/mortalidade , Citosina/administração & dosagem , Citosina/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Organofosfonatos/efeitos adversos , Taxa de Sobrevida
19.
Korean J Intern Med ; 34(2): 375-382, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29237252

RESUMO

BACKGROUND/AIMS: Anti-thymocyte globulin (ATG) treatment for acute T-cell mediated rejection (TCMR) can increase the risk of cytomegalovirus (CMV) infection. We aimed to evaluate the effect of valacyclovir prophylaxis against CMV infection after ATG administration as anti-rejection therapy. METHODS: We retrospectively analyzed 55 kidney transplant recipients (KTRs) receiving ATG for steroid resistant TCMR. In all KTRs, we used intravenous ganciclovir during ATG injection. In 34 KTRs treated before July 2013, we performed preemptive therapy for CMV infection after ATG therapy. They were regarded as the historic control group (CONT). After July 2013, we used valacyclovir maintenance for 1 month after ATG therapy in 21 patients (VAL). The primary outcome was the incidence of CMV infection, and the secondary outcomes were subsequent acute rejection, and graft and patient outcome. RESULTS: Valacyclovir prophylaxis significantly reduced the incidence of CMV infection (VAL, 9.6% vs. CONT, 67.6%; p < 0.001), and CMV-free survival rate was higher in the VAL group compared to the CONT group (p = 0.009). In the VAL group, two cases of CMV infection were limited to CMV viremia, but CMV disease or syndrome (n = 3) was detected in the CONT group. There was no difference in graft failure (CONT, 70.5% vs. VAL, 47.6%; p = 0.152), incidence of subsequent rejection after ATG treatment (CONT, 41.1% vs. VAL, 33.3%; p = 0.776), and graft or patient survival between the two groups. There were no major adverse events associated with valacyclovir prophylaxis. CONCLUSION: In conclusion, valacyclovir prophylaxis is effective in the prevention of CMV infection after ATG treatment for steroid resistant TCMR.


Assuntos
Soro Antilinfocitário/efeitos adversos , Antivirais/uso terapêutico , Infecções por Citomegalovirus/prevenção & controle , Rejeição de Enxerto/tratamento farmacológico , Valaciclovir/uso terapêutico , Adulto , Infecções por Citomegalovirus/etiologia , Feminino , Rejeição de Enxerto/imunologia , Humanos , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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