Multidrug‐resistant Gram‐negative bacterial infections in solid organ transplant recipients—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of infections due to multidrug‐resistant (MDR) Gram‐negative bacilli in the pre‐ and post‐transplant period. MDR Gram‐negative bacilli, including carbapenem‐resistant Enterobacteriaceae, MDR Pseudomonas aeruginosa, and carbapenem‐resistant Acinetobacter baumannii, remain a threat to successful organ transplantation. Clinicians now have access to at least five novel agents with activity against some of these organisms, with others in the advanced stages of clinical development. No agent, however, provides universal and predictable activity against any of these pathogens, and very little is available to treat infections with MDR nonfermenting Gram‐negative bacilli including A baumannii. Despite advances, empiric antibiotics should be tailored to local microbiology and targeted regimens should be tailored to susceptibilities. Source control remains an important part of the therapeutic armamentarium. Morbidity and mortality associated with infections due to MDR Gram‐negative organisms remain unacceptably high. Heightened infection control and antimicrobial stewardship initiatives are needed to prevent these infections, curtail their transmission, and limit the evolution of MDR Gram‐negative pathogens, especially in the setting of organ transplantation.     

Changing trends in the aetiology,treatment and outcomes of bloodstream infection occurring in the first year after solid organ transplantation: a single‐centre prospective cohort study

To analyse trends in the aetiology, treatment and outcomes of bloodstream infection (BSI) within the first year post‐transplant over the last 10‐year period, we prospectively recorded all episodes of BSI occurring in solid organ transplant (SOT) recipients during the first year post‐transplant from 2007 to 2016. Trends of factors were analysed by 2‐year periods. Of 475 consecutive episodes of BSI, 218 occurred within a year of SOT in 178 SOT recipients. Gram‐positive BSI decreased over time (40.5–2.2%). In contrast, there was a steady increase in Gram‐negative bacilli (GNB) BSI (54.1–93.3%; P < 0.001), mainly due to Pseudomonas aeruginosa (2.4–20.4%) and Klebsiella pneumoniae (7.1–26.5%). Multidrug‐resistant (MDR) GNB (4.8–38.8%; P < 0.001) rose dramatically, especially due to extended‐spectrum β‐lactamase (ESBL) production (7.1–34.7%). There was a sharp rise in the use of carbapenems, both as empirical (11.9–55.3%; P < 0.001) and as targeted antibiotic treatment (11.9–46.9%; P < 0.001). In conclusion, today, GNB are the leading causative agents of BSI in SOT recipients within the first year after SOT. In addition, MDR GNB have emerged mainly due to ESBL‐producing strains. In spite of these changes, length of hospital stay, days of treatment and mortality have remained stable over time.     

A novel Online‐to‐Offline (O2O) model for pre‐exposure prophylaxis and HIV testing scale up

Introduction : PrEP awareness and uptake among men who have sex with men (MSM) and transgender women (TG) in Thailand remains low. Finding ways to increase HIV testing and PrEP uptake among high‐risk groups is a critical priority. This study evaluates the effect of a novel Adam's Love Online‐to‐Offline (O2O) model on PrEP and HIV testing uptake among Thai MSM and TG and identifies factors associated with PrEP uptake. Methods : The O2O model was piloted by Adam's Love ( www.adamslove.org ) HIV educational and counselling website. MSM and TG reached online by PrEP promotions and interested in free PrEP and/or HIV testing services contacted Adam's Love online staff, received real‐time PrEP eCounseling, and completed online bookings for receiving services at one of the four sites in Bangkok based on their preference. Auto‐generated site‐ and service‐specific e‐tickets and Quick Response (QR) codes were sent to their mobile devices enabling monitoring and check‐in by offline site staff. Service uptake and participant's socio‐demographic and risk behaviour characteristics were analyzed. Factors associated with PrEP uptake were assessed using multiple logistic regression. Results : Between January 10th and April 11th, 2016, Adam's Love reached 272,568 people online via the PrEP O2O promotions. 425 MSM and TG received eCounseling and e‐tickets. There were 325 (76.5%) MSM and TG who checked‐in at clinics and received HIV testing. Nine (2.8%) were diagnosed with HIV infection. Median (IQR) time between receiving the e‐ticket and checking‐in was 3 (0–7) days. Of 316 HIV‐negative MSM and TG, 168 (53.2%) started PrEP. In a multivariate model, higher education (OR 2.30, 95%CI 1.14–4.66; p = 0.02), seeking sex partners online (OR 2.05, 95%CI 1.19–3.54; p = 0.009), being aware of sexual partners’ HIV status (OR 2.37, 95%CI 1.29–4.35; p = 0.008), ever previously using post‐exposure prophylaxis (PEP) (OR 2.46, 95%CI 1.19–5.09; p = 0.01), and enrolment at Adam's Love clinic compared to the other three sites (OR 3.79, 95%CI 2.06–6.95; p < 0.001) were independently associated with PrEP uptake. Conclusions : Adam's Love O2O model is highly effective in linking online at‐risk MSM and TG to PrEP and HIV testing services, and has high potential to be replicated and scaled up in other settings with high Internet penetration among key populations.     

Hepatic encephalopathy and post‐transplant hyponatremia predict early calcineurin inhibitor‐induced neurotoxicity after liver transplantation

Early calcineurin inhibitor‐induced neurotoxicity (ECIIN) is considered when neurological symptoms occur within 4 weeks after liver transplantation (LT). Risk factors and clinical outcome of ECIIN remain largely unknown. We sought to estimate the incidence, risk factors, and outcome of ECIIN after LT. We retrospectively evaluated 158 patients that underwent LT in a 2‐year period and received immunosuppression with calcineurin inhibitors (CNI) and prednisone. ECIIN was considered when moderate/severe neurological events (after excluding other etiologies) occurred within 4 weeks after LT and improved after modification of CNI. Demographic and clinical variables were analyzed as risk factors. Twenty‐eight (18%) patients developed ECIIN and the remaining 130 patients were analyzed as controls. History of pre‐LT hepatic encephalopathy (OR 3.16, 95% CI 1.29–7.75, P = 0.012), post‐LT hyponatremia (OR 3.34, 95% CI 1.38–9.85, P = 0.028), and surgical time >7 h (OR 2.62, 95% CI 1.07–6.41, P = 0.035) were independent factors for ECIIN. Acute graft rejection and infections were more frequent in the ECIIN group. In addition, length of stay was longer in ECIIN patients. In conclusion, pre‐LT hepatic encephalopathy, surgical time >7 h, and post‐LT hyponatremia are risk factors for ECIIN. Clinical complications and a longer hospital stay are associated with ECIIN development.     

Mannose‐Binding Lectin–Deficient Donors Increase the Risk of Bacterial Infection and Bacterial Infection–Related Mortality After Liver Transplantation

Mannose‐binding lectin (MBL) is synthesized by the liver and binds to microbes. MBL2 gene polymorphisms produce intermediate/low/null or normal MBL serum levels (MBL‐deficient or MBL‐sufficient phenotypes, respectively). We aimed to evaluate the incidence and severity of infection, rejection, and survival within 1 year after liver transplantation (LT) according to donor and recipient MBL2 gene polymorphisms. A repeated‐event analysis for infection episodes (negative binomial regression, Andersen–Gill model) was performed in 240 LTs. Four hundred twenty‐eight infectious episodes (310 bacterial, 15 fungal, 65 cytomegalovirus [CMV]‐related, and 38 viral non–CMV‐related episodes) and 48 rejection episodes were recorded. The main bacterial infections were urinary (n = 82, 26%) and pneumonia (n = 69, 22%). LT recipients of MBL‐deficient livers had a higher risk of bacterial infection (incidence rate ratio [IRR] 1.48 [95% confidence interval 1.04–2.09], p = 0.028), pneumonia (IRR 2.4 [95% confidence interval 1.33–4.33], p = 0.013), and septic shock (IRR 5.62 [95% confidence interval 1.92–16.4], p = 0.002) compared with recipients of MBL‐deficient livers. The 1‐year bacterial infection–related mortality was higher in recipients of MBL‐deficient versus MBL‐sufficient livers (65.8% vs. 56.1%, respectively; p = 0.0097). The incidence of rejection, viral, or fungal infection was similar in both groups. Recipient MBL2 genotype did not significantly increase the risk of bacterial infection. LT recipients of MBL‐deficient livers have a higher risk of bacterial infection, pneumonia, septic shock, and 1‐year bacterial infection–related mortality after LT.     

Neurological events after liver transplantation: a single‐center experience

The aim of this study was to identify potential risk factors linked to neurologic events (NE) occurring after liver transplantation (LT) and use them to construct a model to predict such events. From odds ratios (OR) of risk factors, a scoring system was assessed using multivariate regression analysis. Forty‐one of 307 LT patients presented NE (13.3%), with prolonged hospital stay and decreased post‐LT survival. On multivariate analysis, factors associated with NE included: severe pre‐LT ascites OR 3.9 (1.80–8.41; P = 0.001), delta sodium ≥12 mEq/l OR 3.5 (1.36–8.67; P = 0.01), and post‐LT hypomagnesemia OR 2.9 (1.37–5.98; P = 0.005). Points were assigned depending on ORs as follows: ascites 4 points, and hypomagnesemia and delta sodium ≥12 mEq/l, 3 points each (score range = 0–10 points). ROC curve analysis suggested good discriminative power for the model, with a c‐statistic of 0.72 (CI 0.62–0.81; P < 0.0001), best performance for a cutoff value >3 points (71% sensitivity, 60% specificity). NE risk increased progressively from 6.4%, to 10.3%, 12.8%, 31.5% and 71.0% as scores rose from 0 to 3, 4, 6–7 and 10 cumulative points, respectively. The score described helps to identify patients potentially at risk for neurologic events, and its prevention would decrease morbidity and mortality after LT.     

Histologically proven non‐alcoholic fatty liver disease and clinically related factors in recipients after liver transplantation

Non‐alcoholic fatty liver disease (NAFLD) affects a substantial proportion of the world population, and its prevalence has been increasing. The study was aimed at evaluating the prevalence and peri‐transplant risk factors for post‐liver transplantation (LT) NAFLD. A retrospective review was performed for adult recipients who underwent late protocol biopsy (>1 yr after LT) between August 2010 and December 2012. Hepatic steatosis was reviewed and graded by hepatopathologists, and the peri‐transplant factors were analyzed for relationships to histologically proven NAFLD. Total 166 biopsies had been performed in 156 recipients. NAFLD was present in 27.1% at a mean period of 35.4 months between LT and biopsy, moderate and severe steatosis (≥33%) consisted of 28.9%. In multivariate analysis, pre‐LT alcoholic cirrhosis (odds ratio [OR] 8.031, p = 0.003), obesity at biopsy (OR 3.873, p = 0.001), and preexisting donor graft steatosis (OR 3.147, p = 0.022) were significant risk factors for post‐LT NAFLD. In conclusion, NAFLD represented a considerable portion of recipients, but this prevalence was not higher than those for general population. Three risk factors were significantly related to post‐LT NAFLD, and recipients with those factors should be monitored for NAFLD. Furthermore, possible progression to non‐alcoholic steatohepatitis (NASH) or fibrosis and metabolic syndrome should be considered in future studies.     

Interleukin‐17 and Toll‐like Receptor 10 genetic polymorphisms and susceptibility to large joint osteoarthritis

Primary osteoarthritis (OA) is the most common type of a joint disease. It has a polygenic risk inheritance pattern and affects older people. The etiology of this disease is not fully understood. The aim of this study was to investigate the associations between polymorphisms in pro‐inflammatory interleukin‐17 (IL17A and IL17F) and anti‐inflammatory Toll‐like Receptor 10 (TLR10) genes with the risk for development of advanced stage hip and knee primary OA in the Croatian population. A total of 500 OA patients and 597 controls were genotyped for IL17A SNP (rs2275913), IL17F SNPs (rs763780 and rs1889570), and TLR10 (rs11096957) genes. The allelic and genotypic frequencies of IL17F SNP (rs763780) showed statistically significant differences in comparisons of controls with hip—but not knee—OA patients. The major allele (T) of rs763780 was associated with the lower risk for developing hip OA (p = 7.9 × 10^?4, OR = 0.45, 95%CI = 0.27–0.74), whereas the minor allele (C) was associated with susceptibility to hip OA (p = 7.9 × 10^?4, OR = 2.24, 95%CI = 1.35–3.72). The genotype T/T was associated with the protection to hip OA (p = 3.9 × 10^?4, OR = 0.41, 95%CI = 0.24–0.70), and, lastly, the genotype T/C was associated with the higher risk to acquiring hip OA (p = 2.6 × 10^?4, OR = 2.50, 95%CI = 1.47–4.25). TLR10 SNP rs11096957 was found significantly associated with predisposition to hip OA (p = 0.04, OR = 1.41, 95%CI = 1.02–1.94) but not knee OA. Our findings suggest that hip OA in Croatian population might have a different genetic risk regarding the IL17 and TLR10 gene locus than knee OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1684–1693, 2018.

     

Epidemiology,risk factors,and impact of bacterial infections on outcomes for pancreatic grafts

We aimed to determine the epidemiology, risk factors, and impact of bacterial infection on pancreatic function after pancreas transplantation. Data for pancreas transplant recipients were retrospectively reviewed between 2000 and 2014 for at least 1 year. We collected and analyzed post‐transplant data for bacterial infection, morbidity, and mortality. During the study period, 312 pancreas transplants were performed. In total, 509 episodes of bacterial infection were diagnosed in 191 patients (61%). Multidrug‐resistant (MDR) organisms were present in 173 of the 513 isolated microorganisms (33%). Risk factors independently associated with bacterial infection were acute allograft rejection (OR 1.7, 95%CI 1.1‐3), the need for post‐transplant hemodialysis, (OR 5.3, 95%CI 1.8‐15.7) and surgical re‐intervention (OR 2.8, 95%CI 1.5‐5.1), which was also considered a risk factor for infections caused by MDR bacteria. Graft survival was associated with the occurrence of one or more episodes of bacterial infection (log‐rank test = 0.009). Surgical re‐intervention was independently associated with graft loss (OR 2.5, 95%CI 1.3‐4.7). To conclude, pancreas recipients frequently experienced bacterial infections associated with the need for hemodialysis or surgical re‐intervention. Infection by MDR organisms is a growing concern in these patients and was related to graft survival. Graft loss was independently associated with surgical re‐intervention.     

Pre‐operative trans‐catheter arterial chemo‐embolization increases hepatic artery thrombosis after liver transplantation – a retrospective study

Little is known about nonsurgical risk factors for hepatic artery thrombosis (HAT ) after liver transplantation (LT ). We determined risk factors for HAT occurring within 90 days post‐LT and analysed the effect of HAT on graft and patient survival. Donor and recipient demographics, surgery‐related data and outcome in transplants complicated by thrombosis (HAT +) and their matched controls (HAT ?) were compared. Risk factors were assessed by univariate logistic regression. Median (IQR ) is given. A total of 25 HAT occurred among 1035 adult LT (1/1997–12/2014) and 50 controls were manually matched. Donor and recipient demographics were similar. Pre‐LT trans‐catheter arterial chemo‐embolization (TACE ) was more frequent in HAT + (HAT + 20% vs. HAT ? 4%, P = 0.037). HAT + had longer implantation [HAT + 88 min (76–108) vs. HAT ? 77 min (66–93), P = 0.028] and surgery times [HAT + 6.25 h (5.18–7.47) vs. HAT ? 5.25 h (4.33–6.5), P = 0.001]. Early graft dysfunction and sepsis were more frequent in HAT + and hospitalization longer. TACE had the greatest odds ratio in unadjusted analysis (OR : 6, 95% CI : 1.07–33.53, P = 0.03). All but seven grafts were lost after HAT (HAT + 72% vs. HAT ? 36%, P = 0.003); however, patient survival was unaffected (HAT + 79.8% vs. HAT ? 76%, P = 0.75). LT candidates undergoing TACE are at risk of developing HAT early after transplant.     

Strongyloides stercoralis infection in human immunodeficiency virus‐infected patients and related risk factors: A systematic review and meta‐analysis

Strongyloidiasis is caused by nematode infections of the genus Strongyloides, mainly Strongyloides stercoralis, and affects tens of millions of people around the world. S. stercoralis hyperinfection and disseminated strongyloidiasis are unusual but potentially fatal conditions mostly due to Gram‐negative bacteremia and sepsis, primarily affecting immunocompromised patients. Infections with immunosuppressive viruses such as human immunodeficiency virus (HIV) and Human T‐cell leucemia virus type 1 (HTLV‐1) have been reported as risk factors for strongyloidiasis. Hyperinfection syndrome has been described in HIV‐positive patients following the use of corticosteroids or during immune reconstitution inflammatory syndrome (IRIS). In this research, we conducted a global systematic review and meta‐analysis to assess the seroprevalence and odds ratios (ORs) of S. stercoralis infections in HIV‐infected patients. A total of 3,649 records were screened, 164 studies were selected and evaluated in more detail, and 94 studies were included in the meta‐analysis. The overall pooled prevalence of S. stercoralis infection in HIV positive patients was 5.1% (CI95%: 4%–6.3%), and a meta‐analysis on six studies showed that with a pooled OR of 1.79 (CI95%: 1.18%–2.69%) HIV‐positive men are at a higher risk of S. stercoralis infections (p < .0052) compared to HIV positive women.     

Risk factors and outcome in ICU-acquired infections

Background: Nosocomial infections are common in intensive care units (ICU). The objectives of this study were to determine risk factors of ICU‐acquired infections, and potential mortality attributable to such infections. Methods: An observational study was performed in a 10‐bed multidisciplinary ICU. For a period of 27 months, all patients admitted for ≥48 h were included. Infections were diagnosed according to Centers for Disease Control and Prevention definitions. Airway colonization was explored by molecular typing. Risk factors for infection were determined by multivariable logistic regression. Survival was analyzed with time‐varying proportional hazards regression. Results: Of 278 patients, 81 (29%) were infected: urinary tract infections in 39 patients (14%), primary bloodstream infections in 25 (9%), surgical site infections in 22 (8%) and pneumonia in 21 (8%). Of the total of 147 episodes, Gram‐negative bacilli were isolated in 90, Gram‐positive cocci in 49 and Candida sp. in 25. Risk factors for pneumonia were mechanical ventilation [odds ratio (OR=7.9, CI 1.8–35), lack of enteral nutriment (OR=8.0, CI 1.4–45) and length of time at risk (OR=1.8, CI 1.2–2.8), while gastric acid inhibitors did not affect the risk (OR=0.99, CI 0.32–3.0). Transmission of bacteria from the stomach to the airway was not confirmed. The risk of death was increased as patients were infected with pneumonia [hazard ratio (HR)=3.6; CI: 1.6–8.1], or primary bloodstream infection (HR=2.5; CI: 1.2–5.4), independent of age and disease severity. Conclusions: Mortality was increased by ICU‐acquired pneumonia and primary bloodstream infections. Our findings did not support the gastro‐pulmonary hypothesis of ICU‐acquired pneumonia. The proposition that blood transfusions increase the risk of ICU‐acquired nosocomial infections was not supported.     

Mortality predictors in recipients developing acute respiratory distress syndrome due to pneumonia after kidney transplantation

Background: The aim of the present study was to investigate the risk factors related to hospital mortality due to infection in kidney recipients with ARDS meeting the Berlin definition.

Methods: Univariate and multivariate logistic regression analysis were used to confirm the independent risk factors related to infection-associated mortality.

Results: From January 2001 to August 2014, a total of 94 recipients with acute respiratory dress syndrome (ARDS) caused by pneumonia following kidney transplantation were enrolled in the present study. The most common type of infection was bacterial (52/94; 55.3%), viral (25/94; 26.6%), and polymicrobial (14/94; 14.9%). The most common ARDS was diagnosed within 6 months after transplantation (76/94; 80.9%). There were 39 deaths in these recipients (39/94; 41.5%). Eleven (11.7%) patients had mild, 47 (50.0%) moderate, and 36 (38.3%) severe ARDS; mortality was 27.3, 27.7, and 63.9%, respectively. The independent predictors of infection-related mortality were serum creatinine level >1.5?mg/dL at ARDS onset (OR 3.5 (95%CI 1.2–10.1), p?=?0.018) and severe ARDS (OR 3.6 (95%CI 1.4–9.7), p?=?0.009) in the multivariate analysis.

Conclusion: Infection-related mortality in kidney transplant patients with ARDS was associated with high serum creatinine level and severe ARDS.     

Rapidity of fibrosis progression in liver transplant recipients with recurrent hepatitis C is influenced by toll‐like receptor 3 polymorphism

Liver transplantation activates the innate immune system through toll‐like receptors (TLRs), potentially leading to allograft rejection and graft failure. We evaluated the association of single‐nucleotide polymorphisms in TLR genes with the severity of hepatitis C virus recurrence after liver transplantation (LT). This is a two‐center study of 176 adult patients who received a first LT from deceased donors for hepatitis C virus (HCV) cirrhosis. Eleven polymorphisms were evaluated by real‐time polymerase chain reaction and melting curves analyses: TLR1 (Asp248Ser and Ser602Ile), TLR2 (Arg753Gln), TLR3 (Leu412Phe), TLR4 (Asp299Gly), TLR5 (Arg392Stop), TLR6 (Ser249Pro), TLR7 (Gln11Leu), TLR8 (Met1Val), and TLR9 (−1237T/C and −1486C/T). The CC genotype of TLR3 Leu412Phe in liver recipients was associated with severe recurrence (odds ratio (OR) = 2.01, 95% confidence interval (95% CI) = 1.02‐3.93, p = 0.04). We also analyzed this polymorphism in 72 of their donors but no association was found with severity of HCV recurrence (p = 0.89). Multivariate analysis showed donor age older than 40 yr (OR=2.93; 95% CI = 1.49–5.8, p = 0.002) and the TLR3 Leu412Phe CC genotype (OR=2.02, 95%CI=1.01–4.05, p = 0.046) were independently associated with severe HCV recurrence. Our results show that the TLR3 Leu412Phe CC genotype is independently associated with severity of hepatitis C recurrence after LT.     

Cetuximab‐based therapy vs noncetuximab therapy in advanced or metastatic colorectal cancer: a meta‐analysis of seven randomized controlled trials

Purpose A meta‐analysis was performed to assess the efficacy and safety of cetuximab‐based therapy vs noncetuximab therapy in advanced or metastatic colorectal cancer. Method A total of 4617 patients from seven randomized controlled trials were available for analysis, with 2305 patients in the cetuximab group and 2312 patients in the noncetuximab group. The efficacy data included progression‐free survival (PFS), overall survival (OS) and overall response rate (ORR). The safety data that contained overall grade 3 and 4 adverse events (AEs), specific grade 3 and 4 toxicity such as acneiform rash, cetuximab‐related skin toxicity, diarrhoea, fatigue, neutropenia, hypertension, nausea and hand–foot skin reaction are evaluated. Result There was a significant PFS benefit in favour of cetuximab‐based therapy (HR = 0.68, 95%CI: 0.63 to 0.73) and OS benefit (HR = 0.90, 95%CI: 0.81 to 1.00). The ORR was significantly higher in the cetuximab‐based arm (OR = 2.19, 95% CI: 1.30 to 3.68). The incidence of overall grade 3–4 toxicity was significantly higher in the cetuximab arm compared with the noncetuximab arm (61.2%vs 43.0%, OR = 2.32, 95%CI: 1.59–3.39). This difference was mainly attributed to cetuximab‐related skin toxicity (OR = 5.86, 95%CI: 1.38–24.88), especially acneiform rash (OR = 51.37, 95%CI: 22.75–116.02). In addition, cetuximab resulted in a significant increase in grade 3 and 4 diarrhoea, fatigue and neutropenia, except for hypertension, nausea and hand–foot skin reaction. Conclusion Cetuximab‐based therapy improves PFS and OS resulting in better ORR vs noncetuximab therapy. Its most common and severe AE is skin toxicity that should be predictable and manageable.     

Neutralizing antibodies against Rift Valley fever virus in wild antelope in far northern KwaZulu‐Natal,South Africa,indicate recent virus circulation

Rift Valley fever (RVF) is a zoonotic viral disease of domestic ruminants in Africa and the Arabian Peninsula caused by a mosquito‐borne Phlebovirus. Outbreaks in livestock and humans occur after heavy rains favour breeding of vectors, and the virus is thought to survive dry seasons in the eggs of floodwater‐breeding aedine mosquitoes. We recently found high seroconversion rates to RVF virus (RVFV) in cattle and goats, in the absence of outbreaks, in far northern KwaZulu‐Natal (KZN), South Africa. Here, we report the prevalence of, and factors associated with, neutralizing antibodies to RVFV in 326 sera collected opportunistically from nyala (Tragelaphus angasii) and impala (Aepyceros melampus) culled during 2016–2018 in two nature reserves in the same area. The overall seroprevalence of RVFV, determined using the serum neutralization test, was 35.0% (114/326; 95%CI: 29.8%–40.4%) and tended to be higher in Ndumo Game Reserve (11/20; 55.0%; 95%CI: 31.5%–76.9%) than in Tembe Elephant Park (103/306; 33.6%; 95%CI: 28.4%–39.3%) (p = .087). The presence of antibodies in juveniles (6/21; 28.6%; 95%CI: 11.3%–52.2%) and sub‐adults (13/65; 20.0%; 95%CI: 11.1%–37.8%) confirmed that infections had occurred at least until 2016, well after the 2008–2011 RVF outbreaks in South Africa. Odds of seropositivity was higher in adults than in sub‐adults (OR = 3.98; 95%CI: 1.83–8.67; p = .001), in males than in females (OR = 2.66; 95%CI: 1.51–4.68; p = .001) and in animals collected ≤2 km from a swamp or floodplain compared with those collected further away (OR = 3.30; 95%CI: 1.70–6.38; p < .001). Under similar ecological conditions, domestic and wild ruminants may play a similar role in maintenance of RVFV circulation and either or both may serve as the mammalian host in a vector–host reservoir system. The study confirms the recent circulation of RVFV in the tropical coastal plain of northern KZN, providing the basis for investigation of factors affecting virus circulation and the role of wildlife in RVF epidemiology.     

De novo Cancer‐Related Death in Australian Liver and Cardiothoracic Transplant Recipients

Evidence is sparse on the relative mortality risk posed by de novo cancers in liver and cardiothoracic transplant recipients. A retrospective cohort study was conducted in Australia using population‐based liver (n = 1926) and cardiothoracic (n = 2718) registries (1984–2006). Standardized mortality ratios (SMRs) were computed by cancer type, transplanted organ, recipient age and sex. During a median 5‐year follow‐up, de novo cancer‐related mortality risk in liver and cardiothoracic recipients was significantly elevated compared to the matched general population (n = 171; SMR = 2.83; 95% confidence interval [95%CI], 2.43–3.27). Excess risk was observed regardless of transplanted organ, recipient age group or sex. Non‐Hodgkin lymphoma was the most common cancer‐related death (n = 38; SMR = 16.6; 95%CI, 11.87–22.8). The highest relative risk was for nonmelanocytic skin cancer (n = 23; SMR = 49.6, 95%CI, 31.5–74.5), predominantly in males and in recipients of heart and lung transplants. Risk of death from de novo cancer was high in pediatric recipients (n = 5; SMR = 41.3; 95%CI, 13.4–96.5), four of the five deaths were non‐Hodgkin lymphoma. De novo cancer was a leading cause of late death, particularly in heart and liver transplantation. These findings support tailored cancer prevention strategies, surveillance to promote early detection, and guidelines for managing immunosuppression once cancer occurs.     

Clinical analysis of emergency liver transplantation: the role of living donor liver transplantation

The current liver allocation system requires reevaluation because of the advancements in peri‐transplantation care and surgical techniques. And, the role of living donor liver transplantation (LDLT) in an emergency has not been determined yet. Retrospective review of all patients undergoing emergency liver transplantation (LT) from January 2000 to June 2010 was conducted, and clinical data were analyzed. Of the total 505 LTs, 69 patients (13.7%) underwent an emergency LT. Of these, 54 patients (78.3%) underwent LDLT using a right liver, and 15 patients (21.7%) underwent deceased donor liver transplantation (DDLT). The overall hospital mortality was 21.7% (15/69). The leading cause of death after transplantation was sepsis (60.0%). Multivariate analysis demonstrated that a model for end‐stage liver disease (MELD) >33 [hazard ratio (HR), 16.6; 95% confidence interval (CI), 1.443–191.632; p = 0.024] and existence of pre‐transplantation intubation (HR, 18.2; 95% CI, 1.463–225.483; p = 0.024) were independent factors associated with poor survival after emergency LT. LDLT group and DDLT group showed no difference in hospital mortality (p = 0.854) and graft survival (p = 0.861). Thus, MELD score and respiratory insufficiency could be parameters predicting post‐transplant survival. And, LDLT using the right liver could be an appropriate alternative to DDLT in an emergency.