The epidemiology of respiratory viruses (RVs) in lung transplant recipients (LTRs) and the relationship of RVs to lung function, acute rejection (AR) and opportunistic infections in these patients ...are not well known. We performed a prospective cohort study (2009–2014) by collecting nasopharyngeal swabs (NPSs) from asymptomatic LTRs during seasonal changes and from LTRs with upper respiratory tract infectious disease (URTID), lower respiratory tract infectious disease (LRTID) and AR. NPSs were analyzed by multiplex polymerase chain reaction. Overall, 1094 NPSs were collected from 98 patients with a 23.6% positivity rate and mean follow‐up of 3.4 years (interquartile range 2.5–4.0 years). Approximately half of URTIDs (47 of 97, 48.5%) and tracheobronchitis cases (22 of 56, 39.3%) were caused by picornavirus, whereas pneumonia was caused mainly by paramyxovirus (four of nine, 44.4%) and influenza (two of nine, 22.2%). In LTRs with LRTID, lung function changed significantly at 1 mo (p = 0.03) and 3 mo (p = 0.04). In a nested case–control analysis, AR was associated with RVs (hazard ratio HR 6.54), Pseudomonas aeruginosa was associated with LRTID (HR 8.54), and cytomegalovirus (CMV) replication or disease was associated with URTID (HR 2.53) in the previous 3 mo. There was no association between RVs and Aspergillus spp. colonization or infection (HR 0.71). In conclusion, we documented a high incidence of RV infections in LTRs. LRTID produced significant lung function abnormalities. Associations were observed between AR and RVs, between P. aeruginosa colonization or infection and LRTID, and between CMV replication or disease and URTID.
A large prospective study of the epidemiology of respiratory viruses in lung transplant recipients using molecular assays demonstrates a very high incidence of respiratory viral infection and an association between respiratory virus infectious diseases, immediate allograft dysfunction, and the development of acute rejection and opportunistic infection.
The prognostic factors and optimal therapy for invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT) remain poorly studied. We included in this multinational retrospective study ...112 recipients diagnosed with probable (75.0% of cases) or proven (25.0%) IPA between 2000 and 2013. The median interval from transplantation to diagnosis was 230 days. Cough, fever, and expectoration were the most common symptoms at presentation. Bilateral pulmonary involvement was observed in 63.6% of cases. Positivity rates for the galactomannan assay in serum and bronchoalveolar lavage samples were 61.3% and 57.1%, respectively. Aspergillus fumigatus was the most commonly identified species. Six‐ and 12‐week survival rates were 68.8% and 60.7%, respectively, and 22.1% of survivors experienced graft loss. Occurrence of IPA within the first 6 months (hazard ratio HR: 2.29; p‐value = 0.027) and bilateral involvement at diagnosis (HR: 3.00; p‐value = 0.017) were independent predictors for 6‐week all‐cause mortality, whereas the initial use of a voriconazole‐based regimen showed a protective effect (HR: 0.34; p‐value = 0.007). The administration of antifungal combination therapy had no apparent impact on outcome. In conclusion, IPA entails a dismal prognosis among KT recipients. Maintaining a low clinical suspicion threshold is key to achieve a prompt diagnosis and to initiate voriconazole therapy.
Invasive pulmonary aspergillosis presents a high mortality rate in kidney transplant recipients, with diagnosis within the first 6 months posttransplantation and bilateral lung involvement as independent risk factors for mortality.
Objectives
The aim of the study was to investigate the dynamics of cytomegalovirus (CMV) replication and CMV‐specific immune response recovery after antiretroviral treatment (ART) initiation in ...patients with advanced HIV infection.
Methods
A prospective observational study of patients with HIV infection and CD4 counts of < 100 cells/µL was carried out (September 2015 to July 2018). HIV viral load (VL), CD4 count and CMV VL were determined by quantitative polymerase chain reaction (PCR) at baseline and at 4, 12, 24 and 48 weeks, and CMV‐specific immune response was determined by QuantiFERON‐CMV assay at baseline and 48 weeks. All patients were started on ART but only those with CMV end‐organ disease (EOD) received anti‐CMV treatment.
Results
Fifty‐three patients with a median age of 43.6 interquartile range (IQR) 36.7–52.4 years were included in the study. At baseline, the median CD4 count was 30 cells/µL (IQR 20–60 cells/µL) and the median HIV VL was 462 000 HIV‐1 RNA copies/mL (IQR 186 000–1 300 000 copies/mL). At baseline, 32% patients had detectable CMV viraemia but none had detectable CMV viraemia at 48 weeks. Only one of 53 (1.9%) patients developed EOD during follow‐up. Seven (13.2%) patients were lost to follow‐up and six (11.3%) died; none of the deaths was related to CMV. Similar percentages of patients had a CMV‐specific immune response at baseline (71.7%) and at 48 weeks (70.0%). The magnitude of this response tended to increase over time median 1.63 (IQR 0.15–5.77) IU/mL at baseline vs. median 2.5 (IQR 0.1–8.325) IU/mL at 48 weeks; P = 0.11. We did not find any risk factors associated with 48‐week mortality.
Conclusions
Although the prevalence of CMV viraemia in patients with advanced HIV infection remains high, achieving a good immunological recovery through ART is enough to suppress CMV viraemia, without an increased risk of CMV EOD. The prevalence of a CMV‐specific immune response was high and endured over time.
In the context of solid organ transplantation, screening of recipients and organ donors is crucial, and should be performed with great rigour to minimize the reactivation or the risk of transmission ...of certain infectious processes. This review aims to update understanding of the possible pathologies involved, as well as of emerging infections that, as a result of globalization, are gaining increasing prominence on a daily basis.
Background
Urinary tract infection (UTI) is the most common infection in renal transplant patients, but it is necessary to determine the risk factors for bacterial UTI in recipients of other solid ...organ transplants (SOTs), as well as changes in etiology, clinical presentation, and prognosis.
Methods
In total, 4388 SOT recipients were monitored in 16 transplant centers belonging to the Spanish Network for Research on Infection in Transplantation (RESITRA). The frequency and characteristics of bacterial UTI in transplant patients were obtained prospectively from the cohort (September 2003 to February 2005).
Results
A total of 192 patients (4.4%) presented 249 episodes of bacterial UTI (0.23 episodes per 1000 transplantation days); 156 patients were kidney or kidney–pancreas transplant recipients, and 36 patients were liver, heart, and lung transplant recipients. The highest frequency was observed in renal transplants (7.3%). High frequency of cystitis versus pyelonephritis without related mortality was observed in both groups. The most frequent etiology was Escherichia coli (57.8%), with 25.7% producing extended‐spectrum β‐lactamase (ESBL). In all transplants but renal, most cases occurred in the first month after transplantation. Cases were uniformly distributed during the first 6 months after transplantation in renal recipients. Age (odds ratio OR per decade 1.1, 95% confidence interval CI 1.02–1.17), female gender (OR 1.74, 95% CI 1.42–2.13), and the need for immediate post‐transplant dialysis (OR 1.63, 95% CI 1.29–2.05) were independent variables associated with bacterial UTI in renal and kidney–pancreas recipients. The independent risk factors identified in non‐renal transplants were age (OR per decade 1.79, 95% CI 1.09–3.48), female gender (OR 1.7, 95% CI 1.43–2.49), and diabetes (OR 1.02, 95% CI 1.001–1.040).
Conclusions
UTI was frequent in renal transplants, but also not unusual in non‐renal transplants. Because E. coli continues to be the most frequent etiology, the emergence of ESBL‐producing strains has been identified as a new problem. In both populations, most cases were cystitis without related mortality. Although the first month after transplantation was a risk period in all transplants, cases were uniformly distributed during the first 6 months in renal transplants. Age and female gender were identified as risk factors for UTI in both populations. Other particular risk factors were the need for immediate post‐transplant dialysis in renal transplants and diabetes in non‐renal transplants.
Background
Cytomegalovirus (CMV)‐negative recipients of a graft from a CMV‐positive donor (D+/R−) are at high risk of CMV disease. Current preventive strategies include universal prophylaxis (UP) and ...preemptive therapy (PT). However, the best strategy to prevent CMV disease and achieve better long‐term outcomes remains a matter of debate.
Methods
We analyzed the incidence of CMV disease and long‐term outcomes including graft dysfunction and patient mortality at 5 years after transplantation with both preventive strategies. High‐risk (D+/R−) kidney and liver transplant recipients from the RESITRA cohort were included.
Results
Of 2410 kidney or liver transplant patients, 195 (8.3%) were D+/R−. The final cohort included 58 liver and 102 kidney recipients. UP was given in 92 patients and 68 received PT; 10.9% and 36.8% developed CMV disease, respectively (P < 0.01). The independent risk factors for CMV disease were PT strategy (hazard ratio HR, 3.30; 95% confidence interval CI, 1.6–6.9), kidney transplantation (HR, 3.8; 95% CI, 1.4–9.9), and cyclosporine immunosuppression (HR, 2.4; 95% CI, 1.2–4.7). PT strategy was also a risk factor for CMV disease in both liver transplantation (HR, 11.0; 95% CI, 1.2–98.7) and kidney transplantation (HR, 2.7; 95% CI, 1.3–6.0), independently. The development of CMV replication during the first 2 years after transplantation was a risk factor for graft dysfunction at 5 years after transplantation (odds ratio, 3.4; 95% CI, 1.3–9.0). Nevertheless, no significant differences were seen in either graft dysfunction or mortality between the 2 strategies.
Conclusions
The study supports the benefit of the UP strategy to prevent CMV disease in D+/R− liver or kidney transplant patients. The development of CMV replication during the first 2 years after transplantation was associated with graft dysfunction at 5 years after transplantation.
Ndondondwane, an Early Iron Age settlement situated on the banks of the Thukela River, KwaZulu-Natal, South Africa, provides a unique record of a single, short-term occupation (c. 1300 to 1200 years ...ago). Several areas associated with different activities had been previously excavated and analysed, yielding various scenarios for the cultural and social organisation of the settlement. Three phases of occupation or cultural horizons have been identified and this paper largely explores the charcoal assemblage from the middle cultural horizon, during the settlement’s maximum extent of occupation. Charcoal was analysed from the central part of the site, represented by a livestock byre (kraal), a meeting place, and a craft production area; as well as the peripheral areas including three domestic middens and a charcoal preparation area. Archaeological charcoal specimens were examined using reflective light microscopy to observe the characteristic anatomical features needed to determine the taxonomic group they represent and subsequently identified by direct comparison with a modern charcoal reference collection and published archaeological charcoal studies. Charcoal was identified as belonging to 15 families, 23 genera, and 29 species of trees with known fuel, construction, and medicinal uses. There was a preference for wood previously known as
Acacia
*
, indicating that this genus was readily available and prolific in the surrounds of the site. Ndondondwane has been extensively investigated in terms of the archaeology, and this together with the anthracology data provides further insight into Early Iron Age settlement location-specific activities, cultural practices, and reasons for abandonment.
Background. To facilitate the design of strategies for prevention of invasive aspergillosis in solid-organ transplant recipients, this study investigates whether the development of early-onset and ...late-onset aspergillosis are related to different risk factors, thereby distinguishing 2 risk populations for this serious complication. Methods. A retrospective case-control study was performed, including 156 cases of proven or probable invasive aspergillosis in patients recruited from 11 Spanish centers since the start of the centers' transplantation programs. Results. Among all patients, 57% had early-onset IA (i.e., occurred during the first 3 months after transplantation). Risk factor analysis in this group identified as significantly associated risk factors a more complicated postoperative period, repeated bacterial infections or cytomegalovirus disease, and renal failure or the need for dialysis. Among patients with late-onset infections (i.e., occurred >3 months after transplantation), who comprised 43% of cases, the patients at risk were older, were in an overimmunosuppressed state because of chronic transplant rejection or allograft dysfunction, and had posttransplantation renal failure. Conclusions. Risk factors in patients with early-onset cases and patients with late-onset cases of posttransplantation invasive aspergillosis are not the same, a fact that could have implications for the preventive approaches used for this infection.
Cytomegalovirus (CMV) is the most frequent infectious complication following solid organ transplantation (SOT). The virus, is responsible for both direct (viral syndrome, hepatitis, pneumonitis, ...colitis, etc.) and indirect effects (rejection, infections by other microorganisms and graft dysfunction). In this evidence-based guideline we deal with the most important aspects of CMV infection in SOT recipients, including pre- and post-transplant diagnosis assessment and risk factors, with special emphasis on the prevention and treatment of this viral infection. Overall, adequate management of CMV infection is a critical aspect of transplant patient care.
Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the ...healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate's phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.
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