[Show abstract][Hide abstract] ABSTRACT: Despite administration of annual influenza vaccination, influenza-associated complications in transplant recipients continue to be an important cause of hospitalization and death. Although influenza vaccination has been proven to be the most effective measure to reduce influenza infection after transplantation, transplant recipients are still vulnerable to influenza infections, with lower serological responses to vaccination compared to the general population. In order to assess the efficacy and safety of an alternative immunization scheme for solid organ transplant recipients, the TRANSGRIPE1-2Study Group aimed to test a booster dose administration 5 weeks after the standard vaccination. The primary objective of this trial was to compare short-term and long-term neutralizing antibody immunogenicity of a booster dose of influenza vaccination to the standard single-dose immunization scheme. Secondary objectives included the evaluation of the efficacy and/or safety, cellular immune response, incidence of influenza infection, graft rejection, retransplant and mortality rates.
[Show abstract][Hide abstract] ABSTRACT: We determined the characteristics of posttransplant tuberculosis and the impact of rifampin-based antituberculosis regimens on outcomes in the current era. Patients comprised 64 transplant recipients with tuberculosis, divided into 2 consecutive cohorts: an earlier cohort (cases occurring from 2003 to 2007) and a later cohort (cases from 2008 to 2011). Patients from the later versus earlier era had tuberculosis develop later after transplant (odds ratio, 1.01; 95% CI, 1.00-1.02; P= .05), were more likely to be liver transplant recipients (odds ratio, 4.52; 95% CI, 1.32-15.53; P= .02), and were more likely to receive tacrolimus-based immunosuppression (odds ratio, 3.24; 95% CI, 1.14-9.19; P= .03). Mortality rate was 10% in the later cohort and 21% in the earlier cohort (P= .20). Rifampin-based treatment was less likely to be used in patients with prior rejection (P= .04). However, neither rejection rate (P= .71) nor mortality (P= .93) after tuberculosis differed between recipients who received rifampin and recipients who did not. Thus, notable changes have occurred in the epidemiological characteristics of tuberculosis in transplant recipients. Overall mortality rate has improved, with about 90% of the patients now surviving after tuberculosis.
[Show abstract][Hide abstract] ABSTRACT: Optimizing HCV genotype 1 therapy in terms of response prediction and tailoring treatment is undoubtedly the cornerstone of treating HIV co-infected patients in clinical practice. Accordingly, our aim was to analyze the predictive value of HCV viral decline for sustained virological response (SVR), measured at a time point as early as week 2 of therapy with pegylated interferon alpha-2a plus ribavirin (Peg-IFN/RBV).
PLoS ONE 01/2014; 9(6):e99468. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It is not known whether the probability of achieving sustained virological response (SVR) can be determined on the basis of the magnitude of HCV viral decline over the first 4 weeks of Peg-IFN/RBV treatment of HIV/HCV co-infected patients who fail to achieve a rapid virological response (RVR).
HIV patients co-infected with HCV genotype 1 naïve to Peg-IFN/RBV treatment were included. HCV viral decline from baseline to week 4 was graded. The positive predictive value (PPV) for SVR was evaluated according to the magnitude of HCV viral decline at week 4.
One hundred and fifty patients were included. Thirty-four (22.6%) patients achieved RVR, 33 of these (PPV [CI 95%]; 97.05% [86.34-99.85]) achieved SVR. In those patients who did not achieve RVR, the probability to achieving SVR was graded according to the magnitude of viral decline at week 4 (>2 log10 [55.5%], >2.5 log10 [73.3%] and >3 log10 [75%]). The combination of undetectable and magnitude of decline (>2.5 log10) had a PPV for SVR of 89.8% (CI 95%; 0.794-0.964).
The combination of undetectable HCV viral load andmagnitude of decline at week 4 has a high PPV for SVR and identified ahigher number of potential Peg-IFN/RBV responders.
The Journal of infection 11/2013; · 4.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the IL28B effect on hepatitis C virus (HCV) decline during first weeks of treatment according to HCV-1 subtypes.
Patients coinfected with HIV/HCV genotype 1 and naive to peginterferon-alpha-2a and ribavirin (Peg-IFN-alpha-2a/RBV) were included. Plasma HCV-RNA was measured at baseline, and then at weeks 1, 2, and 4. HCV-1 subtype (1a or 1b) was determined. HCV viral decline was analyzed according to HCV-1 subtype between baseline and week 1, week 2 and week 4 of treatment. Additionally, we analyzed the effect of the IL28B (rs12979860) genotype on HCV viral decline with HCV-1a and HCV-1b genotype patients (CC versus non-CC).
Two hundred and six patients were included in the study, of whom 113 (54.8%) and 93 (45.2%) were infected by HCV-1a and 1b genotypes, respectively. No differences were found between HCV-1 subtypes in terms of HCV viral decline or rapid virological response rate. The effect of the IL28B-CC genotype on HCV viral decline was observed only among patients infected with HCV-1b at all time points analyzed (week 1: CC 1.53 ± 0.33, non-CC 0.27 ± 0.24, P <0.001; week 2: CC 1.81 ± 0.39, non-CC 0.74 ± 0.39, P = 0.002; week 4: CC 2.97 ± 0.53, non-CC 1.2 ± 0.61, P < 0.001).
Our study suggests that the effect associated with the impact of the IL28B-CC genotype on HCV decline during the first weeks of treatment with Peg-IFN-alpha-2a/RBV differs according to HCV-1 subtype and may be limited to HCV-1b patients.
AIDS (London, England) 07/2013; 27(12):1941-7. · 4.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Globalization and migration patterns have increased the number of donors from countries with high incidence rates of tuberculosis (TB) in low incidence countries, with the subsequent increase in risk of TB transmission to the recipients. METHODS: Retrospective cohort study, including all actual deceased donors in Spanish hospitals between January 1998 and June 2011 and all the recipients who had received an organ from donors identified as TB cases. RESULTS: Six actual donors were identified as TB cases, representing an annual incidence of 30.6 cases/100,000 donors (95% CI, 4-58). Two cases did not become utilized donors, because TB was detected in the organ recovery and were therefore excluded. Annual incidence in utilized donors was 23 cases/100,000 donors (95% CI, 6-59). Annual incidence of the Spanish population in the same period was 17.5 cases/100,000 inhabitants (95% CI, 17-18). Annual incidence in actual donors belonging to the Romanian immigrant community was 2353 cases/100,000 donors (95% CI, 286-8242). Variations in the prophylactic strategy utilized in recipients were observed. TB was transmitted to three recipients (27.3% transmission), two of whom developed active TB. CONCLUSIONS: Incidence of TB in actual donors is greater than that of the general population (P<0.001). The risk of immigrant communities should be grouped according to the real incidence in donors. Transmissibility of TB is high; therefore, transplant teams should be immediately informed when TB donor transmission is suspected to prevent TB in the recipient.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: The aim of this study was to determine the epidemiology and clinical impact of infections in patients awaiting heart transplantation. METHODS: We evaluated all patients considered for a heart transplant in our center over a period of 18 months over a period of 18 months from 2007 to 2009. The patients were followed up for 8 months or until death, transplant, or loss to follow-up. RESULTS: Ninety patients were included in the study. During follow-up, 25 infections were recorded in 22 heart transplant candidates (24.4%). Respiratory infections were the most frequent infection (12 bronchitis; 48.0%), followed by skin and soft tissue infections (four infections; 16.0%), intra-abdominal infections (four infectious diarrhea; 16.0%), bacteremia (three infections; 12.0%), and urinary tract infections (two infections; 2.0%). Age, comorbidity, sex, and diabetes were not found to be risk factors for infection. Twenty-four patients (26.7%) were transplanted during follow-up. Infection before transplantation was not associated with an increased risk of mortality or a higher rate of infection in the immediate post-transplant period. CONCLUSIONS: Infections are common in heart transplant candidates, affecting almost 25% of them. Respiratory tract infections are the most frequent type of infection. However, they are not associated with increased mortality in the immediate post-transplant period.
International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 03/2013; · 2.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: Pegylated interferon plus ribavirin (Peg-IFN/RBV) therapy leads to improvements in liver stiffness measurements (LSM) in hepatitis C virus (HCV)-infected patients. However, the rate of LSM return to normal values in response to Peg-IFN/RBV is unclear. Thus, our aim was to assess the probability and factors associated with LSM normalization in HCV-infected patients receiving Peg-IFN/RBV. METHODS: This prospective observational longitudinal study included 160 HCV-infected patients, 111 (69%) with human immunodeficiency virus and receiving Peg-IFN/RBV, with baseline LSM ≥7kPa. The outcome variable was LSM normalization, i.e. a stable decrease in LSM below 7kPa after starting Peg-IFN/RBV. RESULTS: After starting Peg-IFN/RBV, 56 [35%, 95% confidence interval (95% CI): 28-42%] patients showed LSM normalization. The probability of LSM normalization was 21% (95% CI: 13.2-32.4%) at 12 months, and 51.3% (95% CI: 39.9-63.9%) at 24 months after Peg-INF/RBV initiation for individuals with sustained virological response (SVR), and 8.3% (95% CI: 4-16.6%) at 12 months and 11.3% (95% CI: 6-20.7%) at 24 months for those without SVR (p<0.001). For individuals with LSM ≥7kPa 24 weeks after the pre-planned end of treatment, LSM normalizations were only observed among those with SVR. Achievement of SVR [Hazard ratio (HR, 95% CI): 6.84 (3.39-13.81)] and lack of baseline cirrhosis [HR (95% CI): 4.17 (1.69-10)] were independently associated with LSM normalization after starting Peg-IFN/RBV. CONCLUSIONS: LSM normalizations during Peg-IFN/RBV treatment are more likely, and occur earlier among patients with SVR. In addition, LSM normalizations continue 24 weeks after the scheduled end of therapy, but only among individuals who reach SVR.
Enfermedades Infecciosas y Microbiología Clínica 02/2013; · 1.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Incidence, characteristics, and risk factors for tuberculosis (TB)-associated immune reconstitution inflammatory syndrome (IRS) in solid-organ transplant (SOT) recipients are not known. METHODS: Patients are composed of 64 consecutive SOT recipients with TB followed for 12 months. IRS was defined based on previously proposed criteria. RESULTS: IRS developed in 14% (9/64) of the patients, a median of 47 days after the use of anti-TB therapy. Liver versus other types of organ transplant recipients (adjusted odds ratio [OR], 6.11; 95% confidence interval [CI], 1.08-34.86), prior cytomegalovirus infection (adjusted OR, 5.65; 95% CI, 0.93-34.47), and rifampin use (adjusted OR, 4.56; 95% CI, 0.74-27) were associated with a higher risk of IRS. The presence of more than one factor (liver transplantation, cytomegalovirus infection, and rifampin use) when compared with none of these factors conferred a 19-fold increase in the risk of IRS (P=0.01). Mortality at 1 year after diagnosis was 33.3% in patients with IRS and 17.2% in those without IRS (P=0.31). CONCLUSIONS: IRS was documented in 14% of the SOT recipients with TB. We determined clinically identifiable factors that may be useful in assessing the risk of tuberculosis-associated posttransplantation IRS.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Experience with high-dose ganciclovir for the management of resistant cytomegalovirus (CMV) replication in transplant patients is limited despite its adoption as an effective therapy by some consensus documents. METHODS: We studied six cases of CMV replication in solid organ transplant patients whose genotypic testing showed mutations associated with different levels of resistance to ganciclovir. All were treated with high-dose intravenous ganciclovir (7.5-10 mg/kg/12 hr) or oral valganciclovir (1350-1800 mg/12 hr) corrected according to creatinine clearance. The virologic response was considered positive if the CMV plasma viral load was undetectable. Safety was evaluated by clinical assessment, including the review of vital signs and laboratory tests. RESULTS: All patients had asymptomatic replication, except one who had digestive disease. Four patients received universal prophylaxis with valganciclovir. Two patients received preemptive therapy with valganciclovir for individual episodes of replication. Two of the six patients received steroid boluses before the episode of replication by resistant CMV. All patients responded to treatment, including those with mutations associated with a high level of ganciclovir resistance. Four patients had neutropenia (<1.5 × 10/L), but only one received treatment. CONCLUSIONS: High-dose ganciclovir/valganciclovir can be an option in the treatment of resistant CMV replication and could be considered an alternative treatment in nonsevere patients for whom the use of foscarnet should be avoided. The toxicity of this regimen does not appear to limit its use.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the influence of the presence of the killer cell immunoglobulin-like receptor (KIR) 3DS1 on HCV treatment response in HIV/HCV genotype 1 co-infected patients.
HIV/HCV co-infected patients were included. KIR3DS1, their specific HLA-B ligands and IL28B gene were genotyped. Reductions of plasma HCV RNA levels between baseline and week 1, week 2 and week 4 were analyzed for IL28B genotype and KIR3DS1 (HLA Bw4 or Bw6). Rapid and sustained virological response (RVR and SVR) rates were also analyzed.
Sixty HIV/HCV genotype 1 co-infected patients were included. Patients with KIR3DS1 and Bw4 had higher rates of HCV viral decline than those who were not carriers of KIR3DS1 (week1: p = 0.01; week2: p = 0.038; week 4: p = 0.03). Patients carrying KIR3DS1/Bw4 had higher rates of RVR and SVR than those who did not carry KIR3DS1 (RVR: 46.15% versus 17.02%, p = 0.012; SVR: 63.6% versus 13 26.5%, p = 0.031). With respect to patients carrying the IL28B-CC genotype, those with KIR3DS1/Bw4 had greater rates of HCV viral clearance (week1: p<0.001; week2: p = 0.01; week 4: p = 0.02), RVR (p = 0.015) and SVR (p = 0.029) than those not carrying KIR3DS1.
Our results show that the KIR3DS1 genotype has a positive effect on HCV viral clearance during the first weeks of Peg-IFN/RBV treatment in HCV/HCV co-infected patients bearing genotype 1, and higher RVR and SVR rates.
PLoS ONE 01/2013; 8(4):e61992. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Human cytomegalovirus (HCMV) infection causes significant morbidity and mortality after hematopoietic stem cell transplantation (HSCT). In this work, we characterized the phenotype and interferon-gamma (INF-γ) production of HCMV-specific T cells using QuantiFERON-HCMV assay in 26 patients 6 months after HSCT. We analysed whether these two parameters were associated with clinical variables. Our results showed that the patients receiving stem cells from donors ≥40 years old were 12 times more likely to have HCMV-specific CD8+ T cells with "differentiated phenotype" (CD45RA+CCR7+ ≤6.7% and CD28+ ≤30%) than patients grafted from donors <40 years old (OR = 12; P = 0.014). In addition, a detectable IFN-γ production in response to HCMV peptides (cutoff 0.2 IU/mL IFN-γ; "reactive" QuantiFERON-HCMV test) was statistically associated with HCMV replication after transplantation (OR = 11; P = 0.026), recipients ≥40 versus <40 years old (OR = 11; P = 0.026), and the use of peripheral blood versus bone marrow as stem cell source (OR = 17.5; P = 0.024). In conclusion, donor age is the only factor significantly associated with the presence of the "differentiated phenotype" in HCMV-specific CD8+ T cells, whereas HCMV replication after transplantation, recipient age, and stem cell source are the factors associated with the production of IFN-γ in response to HCMV epitopes.
Clinical and Developmental Immunology 01/2013; 2013:347213. · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several studies have reported that a significant number of HIV patients not co-infected with HCV/HBV develop liver damage of uncertain origin (LDUO). The objective of our study was to evaluate the incidence of and risk factors for the development of LDUO in HIV infected patients not co-infected with HCV/HBV.
Prospective longitudinal study that included HIV-infected patients free of previous liver damage and viral hepatitis B or C co-infections. Patients were followed up at 6-monthly intervals. Liver stiffness was measured at each visit. Abnormal liver stiffness (ALS) was defined as a liver stiffness value greater than 7.2 kPa at two consecutive measurements. For patients who developed ALS, a protocol was followed to diagnose the cause of liver damage. Those patients who could not be diagnosed with any specific cause of liver disease were diagnosed as LDUO and liver biopsy was proposed.
210 patients matched the inclusion criteria and were included. 198 patients completed the study. After a median (Q1-Q3) follow-up of 18 (IQR 12-26) months, 21 patients (10.6%) developed ALS. Of these, fifteen patients were diagnosed as LDUO. The incidence of LDUO was 7.64 cases/100 patient-years. Histological studies were performed on ten (66.6%) patients and all showed liver steatosis. A higher HOMA-IR value and body mass index were independently associated with the development of LDUO.
We found a high incidence of LDUO in HIV-infected patients associated with metabolic risk factors. The leading cause of LDUO in our study was non-alcoholic fatty liver disease.
PLoS ONE 01/2013; 8(7):e68953. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and objetiveTo determine clinical variables to distinguish invasive pulmonary aspergillosis (IPA) from colonization in patients with chronic pneumopathies with positive culture of Aspergillus spp. in respiratory samples.Patients and methodsRetrospective cohort study including patients with respiratory isolations of Aspergillus spp. during a period of 10 years. IPA was evaluated according to the Bulpa criteria. Clinical variables were collected and a multiple logistic regression analysis was carried out.ResultsEighty-three patients with isolation of Aspergillus spp. from respiratory samples were included; 68.7% (n = 57) of the patients had chronic obstructive pulmonary disease, 18% (n = 15) pulmonary fibrosis and 13.3% (n = 11) bronchial asthma. Twenty-two patients (26.6%) had IPA. The use of fluconazole (OR 4.49; CI 95% 1.5-13.4; P = .007), severe respiratory failure (OR 4.64; CI 95% 1.46-14.72; P = .009) and hospitalization time (OR 1.05; CI 95% 1.01-1.1; P = .006) were associated with IPA.Conclusions
Prior use of fluconazole, severe respiratory failure and hospitalization time are associated with IPA in patients with chronic pneumopathies with respiratory isolation of Aspergillus spp.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND AND OBJETIVE: To determine clinical variables to distinguish invasive pulmonary aspergillosis (IPA) from colonization in patients with chronic pneumopathies with positive culture of Aspergillus spp. in respiratory samples. PATIENTS AND METHODS: Retrospective cohort study including patients with respiratory isolations of Aspergillus spp. during a period of 10 years. IPA was evaluated according to the Bulpa criteria. Clinical variables were collected and a multiple logistic regression analysis was carried out. RESULTS: Eighty-three patients with isolation of Aspergillus spp. from respiratory samples were included; 68.7% (n=57) of the patients had chronic obstructive pulmonary disease, 18% (n=15) pulmonary fibrosis and 13.3% (n=11) bronchial asthma. Twenty-two patients (26.6%) had IPA. The use of fluconazole (OR 4.49; CI 95% 1.5-13.4; P=.007), severe respiratory failure (OR 4.64; CI 95% 1.46-14.72; P=.009) and hospitalization time (OR 1.05; CI 95% 1.01-1.1; P=.006) were associated with IPA. CONCLUSIONS: Prior use of fluconazole, severe respiratory failure and hospitalization time are associated with IPA in patients with chronic pneumopathies with respiratory isolation of Aspergillus spp.
[Show abstract][Hide abstract] ABSTRACT: A case of recurrent cytomegalovirus reactivations in a cytomegalovirus-seropositive woman who received allogeneic cord blood transplantation is described. Thirteen months post-transplantation CD3+ T cells were extremely low whereas natural killer cells represented 66% of total lymphocytes. She showed defective thymic function that might contribute to the onset of valganciclovir resistance.
Clinical and vaccine Immunology: CVI 10/2012; · 2.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Clostridium difficile-associated disease (CDAD) is the most common cause of nosocomial diarrhea. Information about CDAD in solid organ transplant (SOT) recipients is scarce. To determine its epidemiology and risk factors, we conducted a cohort study in which 4472 SOT patients were prospectively included in the RESITRA/REIPI (Spanish Research Network for the Study of Infection in Transplantation) database between July 2003 and July 2006. Forty-two episodes of CDAD were diagnosed in 36 patients. The overall incidence was 0.94%. Median onset of infection was 31.5 days (range 6-741); in half the cases, onset occurred during the first month after transplantation. In 26% of cases, there was no previous antibiotic use. Independent risk factors for CDAD using Cox regression analysis were previous use of first- and second-generation cephalosporins (HR 3.68; 95%CI 1.8-7.52; P < 0.001), ganciclovir prophylactic use (HR 3.09; 95%CI 1.44-6.62; P = 0.004) and corticosteroid use before transplantation (HR 2.95; 95%CI 1.1-7.9; P = 0.031). There were no deaths related to CDAD. In summary, the incidence of CDAD in SOT was low, most cases were diagnosed soon after transplantation and the prognosis was good.
Transplant International 10/2012; · 3.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Before the advent of the influenza A(H1N1)pdm virus in 2009, the information available about the clinical manifestations and prognosis of influenza in immunosuppressed patients was scarce. With the 2009 pandemic, knowledge of the behavior, severity and importance of antiviral therapy for influenza A infection in immunocompromised hosts has increased considerably. The aim of the present manuscript is to review the main challenges of influenza in the most representative immunosuppressed populations such as solid organ transplant recipients, hematopoietic stem cell transplant recipients, patients with solid and hematological cancer and human immunodeficiency virus infected patients.