Immune Monitoring-Guided Versus Fixed Duration of Antiviral Prophylaxis Against Cytomegalovirus in Solid-Organ Transplant Recipients: A Multicenter, Randomized Clinical Trial.

BACKGROUND: The use of assays detecting cytomegalovirus (CMV)-specific T cell-mediated immunity may individualize the duration of antiviral prophylaxis after transplantation. METHODS: In this randomized trial, kidney and liver transplant recipients from 6 centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving antithymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV ELISpot assay (T-Track CMV); prophylaxis in the intervention group was stopped if the assay was positive. The co-primary outcomes were the proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. Between-group differences were adjusted for CMV serostatus. RESULTS: Overall, 193 patients were randomized (92 in the immune-monitoring group and 101 in the control group), of whom 185 had evaluation of the primary outcome (87 and 98 patients). CMV infection occurred in 26 of 87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32 of 98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference, -0.1; 95% confidence interval [CI], -13.0% to 12.7%; P = .064). The duration of prophylaxis was shorter in the immune-monitoring group (adjusted difference, -26.0 days; 95%, CI, -41.1 to -10.8 days; P < .001). CONCLUSIONS: Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary outcome of CMV infection. CLINICAL TRIALS REGISTRATION: NCT02538172.

Vitamin D deficiency is common in kidney transplant recipients, but is not associated with infections after transplantation.

The relevance of vitamin D for infections after kidney transplantation is poorly defined. 25-OH vitamin D (25-OHD) levels of 135 kidney transplant recipients, enrolled in the Swiss Transplant Cohort Study, were determined peri-transplant and 6 months post-transplant. Logistic regression was used to address the associations of 25-OHD and overall infections and bacterial infections, respectively. For the first 6 months post-transplant, 25-OHD peri-transplant, and for the second period (after 6 to 30 months post-transplant), 25-OHD at 6 months post-transplant was considered. Vitamin D deficiency was common peri-transplant and remained highly prevalent 6 months after transplantation despite frequent supplementation. Median 25-OHD levels increased from 12.0 ng/mL (IQR 5.3-19.5) peri-transplant to 16.5 ng/mL (IQR 10.6-22.6) 6 months post-transplant (P = .005). We did not detect a significant association between 25-OHD and overall infections (adjusted odds ratio (aOR) 1.05, 95% confidence interval (95%CI) 0.44-2.51; aOR 0.67, 95%CI 0.31-1.43) or bacterial infections (aOR 0.79, 95%CI 0.32-1.96; aOR 0.79, 95%CI 0.35-1.75) for the first and second period. To conclude, at both time points, vitamin D deficiency was observed in more than 50% of kidney recipients, albeit an increase in 25-OHD in the longitudinal course was observed. No significant association between 25-OHD and infections was detected.

Usefulness of a systematic approach at listing for vaccine prevention in solid organ transplant candidates.

Solid organ transplant (SOT) candidates may not be immune against potentially vaccine-preventable diseases because of insufficient immunizations and/or limited vaccine responses. We evaluated the impact on vaccine immunity at transplant of a systematic vaccinology workup at listing that included (1) pneumococcal with and without influenza immunization, (2) serology-based vaccine recommendations against measles, varicella, hepatitis B virus, hepatitis A virus, and tetanus, and (3) the documentation of vaccines and serology tests in a national electronic immunization registry (www.myvaccines.ch). Among 219 SOT candidates assessed between January 2014 and November 2015, 54 patients were transplanted during the study. Between listing and transplant, catch-up immunizations increased the patients' immunity from 70% to 87% (hepatitis A virus, P = .008), from 22% to 41% (hepatitis B virus, P = .008), from 77% to 91% (tetanus, P = .03), and from 78% to 98% (Streptococcus pneumoniae, P = .002). Their immunity at transplant was significantly higher against S. pneumoniae (P = .006) and slightly higher against hepatitis A virus (P = .07), but not against hepatitis B virus, than that of 65 SOT recipients transplanted in 2013. This demonstrates the value of a systematic multimodal serology-based approach of immunizations of SOT candidates at listing and the need for optimized strategies to increase their hepatitis B virus vaccine responses.

Vitamin D status and risk of infections after liver transplantation in the Swiss Transplant Cohort Study.

Increasing evidence indicates a role of vitamin D in the immune system affecting response to infections. We aimed to characterize the role of vitamin D status, i.e. deficiency [25-OH vitamin D (25-OHD) <50 nmol/l] and no deficiency (25-OHD ≥50 nmol/l) in incident infections after liver transplantation. In 135 liver transplant recipients, blood samples drawn at time of liver transplantation and 6 months afterwards were used to determine 25-OHD levels. Incident infections episodes were prospectively collected within the Swiss Transplant Cohort Study database. Poisson regression was applied to address associations between vitamin D status and incident infections. Vitamin D deficiency was common at time of transplantation and 6 months afterwards without a significant change in median 25-OHD levels. In univariable analyses, vitamin D deficiency was a risk factor for incident infections in the first 6 months post-transplant incidence rate ratio (IRR 1.52, 95% CI 1.08-2.15, P = 0.018) and for bacterial infections occurring after 6 up to 30 months post-transplant (IRR 2.29, 95% CI 1.06-4.94, P = 0.034). These associations were not detectable in multivariable analysis with adjustment for multiple confounders. Efforts to optimize vitamin D supplementation in liver transplant recipients are needed. Our data question the role of vitamin D deficiency in incident infections.

[The immunosuppressed traveler : vaccination guidelines]. / Voyageur immunosupprimé : recommandations vaccinales.

The number of immunosuppressed travelers has exponentially increased in the past few years. This is a positive development as these patients, owing to much improved management, are now in a condition allowing them to plan activities abroad comparable to healthy persons. However, pre-travel consultation and vaccinations are particularly important to reduce the risks and/or the complications of travel-related diseases. Although we already published a review on this topic in 2013, the recent increase of immunosuppressive agents available in Switzerland justifies this update.

Depuis quelques années, le nombre de voyageurs immunosupprimés ne fait qu'augmenter. Nous pouvons bien entendu nous en réjouir, puisque ces patients bénéficient de traitements efficaces qui leur permettent dorénavant d'envisager une vie et des activités comparables à un individu sain. Si nous voulons conserver ce bénéfice, il est nécessaire de préparer et vacciner au mieux ces patients afin de diminuer leurs risques de pathologies infectieuses liées au voyage ou à l'expatriation dans des zones tropicales. En 2013, nous avions déjà publié une revue sur le sujet, et une réactualisation semblait nécessaire au vu du nombre croissant de traitements immunosuppresseurs disponibles sur le marché suisse.

Bone metabolism dynamics in the early post-transplant period following kidney and liver transplantation.

Bone disease contributes to relevant morbidity after solid organ transplantation. Vitamin D has a crucial role for bone metabolism. Activation of vitamin D depends on the endocrine function of both, liver and kidney. Our study assessed key markers of bone metabolism at time of transplantation and 6 months after transplantation among 70 kidney and 70 liver recipients. In 70 kidney recipients 25-OH vitamin D levels did not differ significantly between peri-transplant (median 32.5nmol/l) and 6 months post-transplant (median 41.9nmol/l; P = 0.272). Six months post-transplant median 1, 25-(OH)2 vitamin D levels increased by >300% (from 9.1 to 36.5ng/l; P<0.001) and median intact parathyroid hormone levels decreased by 68.4% (from 208.7 to 66.0 ng/l; P<0.001). Median ß-Crosslaps (CTx) and total procollagen type 1 amino-terminal propeptide (P1NP) decreased by 65.1% (from 1.32 to 0.46ng/ml; P<0.001) and 60.6% (from 158.2 to 62.3ng/ml; P<0.001), respectively. Kidney recipients with incident fractures had significantly lower levels of 1, 25-(OH)2 vitamin D at time of transplantation and of intact parathyroid hormone 6 months post-transplant. Among 70 liver recipients, 25-OH vitamin D, 1, 25-(OH)2 vitamin D and intact parathyroid hormone levels were not significantly altered between peri-transplant and 6 months post-transplant. Contrary to kidney recipients, median CTx increased by 60.0% (from 0.45 to 0.72 ng/ml; P = 0.002) and P1NP by 49.3% (from 84.0 to 125.4ng/ml; P = 0.001) in the longitudinal course. Assessed biomarkers didn't differ between liver recipients with and without fractures. To conclude, the assessed panel of biomarkers proved highly dynamic after liver as well as kidney transplantation in the early post-transplant period. After kidney transplantation a significant gain in 1, 25-(OH)2 vitamin D combined with a decline in iPTH, CTx and P1NP, whereas after liver transplantation an increase in CTx and P1NP were characteristic.

Assessing environmental conditions of Antarctic footpaths to support management decisions.

Thousands of tourists visit certain Antarctic sites each year, generating a wide variety of environmental impacts. Scientific knowledge of human activities and their impacts can help in the effective design of management measures and impact mitigation. We present a case study from Barrientos Island in which a management measure was originally put in place with the goal of minimizing environmental impacts but resulted in new undesired impacts. Two alternative footpaths used by tourist groups were compared. Both affected extensive moss carpets that cover the middle part of the island and that are very vulnerable to trampling. The first path has been used by tourists and scientists since over a decade and is a marked route that is clearly visible. The second one was created more recently. Several physical and biological indicators were measured in order to assess the environmental conditions for both paths. Some physical variables related to human impact were lower for the first path (e.g. soil penetration resistance and secondary treads), while other biochemical and microbiological variables were higher for the second path (e.g. ß-glucosidase and phosphatase activities, soil respiration). Moss communities located along the new path were also more diverse and sensitive to trampling. Soil biota (Collembola) was also more abundant and richer. These data indicate that the decision to adopt the second path did not lead to the reduction of environmental impacts as this path runs over a more vulnerable area with more outstanding biological features (e.g. microbiota activity, flora and soil fauna diversity). In addition, the adoption of a new route effectively doubles the human footprint on the island. We propose using only the original path that is less vulnerable to the impacts of trampling. Finally from this process, we identify several key issues that may be taken into account when carrying out impact assessment and environmental management decision-making in the Antarctic area.

Pandemic influenza A/H1N1 virus infection in solid organ transplant recipients: a multicenter study.

BACKGROUND: The 2009 novel influenza A/H1N1 virus pandemic did not spare solid organ transplant (SOT) recipients. We aimed to describe the behavior of pandemic influenza infection in a group of SOT recipients in Argentina. METHODS: Data from 10 transplant (Tx) centers were retrospectively collected for SOT that presented with a respiratory illness compatible with pandemic influenza A infection, between May and September 2009. Cases were defined as suspected, probable, or confirmed according to diagnostic method. RESULTS: Seventy-seven cases were included. No significant differences in presenting symptoms, pulmonary infiltrates, and graft involvement were found among 35 suspected, 19 probable, and 23 confirmed cases. The 33 ambulatory cases had significantly more sore throat and headache when compared with 34 cases admitted to medical ward (MW) and 10 admitted to intensive care unit (ICU), 9 of whom required ventilatory support. MW and ICU cases had significantly more dyspnea, hypoxemia, pulmonary infiltrates, and graft dysfunction. Time from onset of symptoms to first visit and to treatment was significantly longer in MW and ICU cases (P=0.008). Coinfections were found in six cases. Most cases received oseltamivir for 5 to 10 days. Six patients (7.8%) died from viral infection at a median of 15 days from admission. No differences in outcome were seen related to the transplanted organ, the immunosuppressive regimen, time from Tx, or confirmation of diagnosis. CONCLUSIONS: Mortality is higher in Tx recipients than in the general population. Poor outcome seems to be related to a delay in the beginning of treatment.

[Chronic meningococcemia]. / Meningococcemia crónica.

Chronic meningococcemia is an unfrequent clinical picture within the spectrum of infections produced by Neisseria meningitidis. It is classically characterized by fever, skin lesions and joint involvement, usually without meningeal involvement, and with blood culture growth of the responsible bacteria. It generally affects previously healthy young people. It is unknown why these patients, unlike patients with Neisseria meningitidis's acute meningitis and with acute meningococcemia, can survive without complications during weeks, in abscence of an useful antibiotic treatment. It has been hypothesized that owing to high susceptibility to beta-lactam antibiotics of Neisseria meningitidis, many cases may be treated inadvertently. We describe a case of chronic meningococcemia in a young woman who presented a classical clinical picture, not recognized initially.

Meningococcemia crónica / Chronic menigococcemia

La meningococcemia crónica es una forma clínica infrecuente dentro del espectro de infecciones producido por Neisseria meningitidis. Clásicamente esta forma clínica se caracteriza por fiebre, lesiones cutáneas, compromiso articular, y desarrollo en hemocultivo de la bacteria responsable, habitualmente con ausencia de compromiso meníngeo. Generalmente afecta a adultos jóvenes previamente sanos. Se desconoce la razón por la cual estos pacientes, a diferencia de los que presentan meningitis aguda por Neisseria meningitidis y meningococcemia aguda, pueden sobrevivir sin complicaciones durante semanas en ausencia de tratamiento antibiótico útil. Se ha planteado que debido a la alta sensibilidad de esta bacteria a los antibióticos beta-lactámicos, muchos casos podrían ser tratados inadvertidamente. Describimos un caso de meningococcemia crónica en una mujer joven que presenta un cuadro clásico no reconocido inicialmente.

Chronic meningococcemia is an unfrequent clinical picture within the spectrum of infections produced by Neisseria meningitidis. It is classically characterized by fever, skin lesions and joint involvement, usually without meningeal involvement, and with blood culture growth of the responsible bacteria. It generally affects previously healthy young people. It is unknown why these patients, unlike patients with Neisseria meningitidis’s acute meningitis and with acute meningococcemia, can survive without complications during weeks, in abscence of an useful antibiotic treatment. It has been hypothesized that owing to high susceptibility to beta-lactam antibiotics of Neisseria meningitidis, many cases may be treated inadvertently. We describe a case of chronic meningococcemia in a young woman who presented a classical clinical picture, not recognized initially.