In 2016, the Transplantation Society of Australia and New Zealand, with the support of the Australian Government Organ and Tissue authority, commissioned a literature review on the topic of infectious disease transmission from deceased donors to recipients of solid organ transplants. The purpose of this review was to synthesize evidence on transmission risks, diagnostic test characteristics, and recipient management to inform best-practice clinical guidelines. The final review, presented as a special supplement in Transplantation Direct, collates case reports of transmission events and other peer-reviewed literature, and summarizes current (as of June 2017) international guidelines on donor screening and recipient management. Of particular interest at the time of writing was how to maximize utilization of donors at increased risk for transmission of human immunodeficiency virus, hepatitis C virus, and hepatitis B virus, given the recent developments, including the availability of direct-acting antivirals for hepatitis C virus and improvements in donor screening technologies. The review also covers emerging risks associated with recent epidemics (eg, Zika virus) and the risk of transmission of nonendemic pathogens related to donor travel history or country of origin. Lastly, the implications for recipient consent of expanded utilization of donors at increased risk of blood-borne viral disease transmission are considered.

BackgroundCytomegalovirus (CMV) establishes a lifelong infection that is efficiently controlled by the immune system; this infection can be reactivated in case of immunosuppression such as following solid organ transplantation. CMV viraemia has been associated with CMV disease, as well as increased mortality and allograft failure. Prophylactic antiviral medication is routinely given to renal transplant recipients, but reactivation during and following cessation of antiviral prophylaxis is known to occur. The aims of this study were to assess the incidence, timing and impact of CMV viraemia in renal transplant recipients and to determine the level of viraemia associated with adverse clinical outcomes.MethodsData from all adult (18 years and over) Western Australian renal transplant recipients transplanted between 1 January 2007 and 31 December 2012 were obtained from the Australia and New Zealand Dialysis and Transplant registry and were supplemented with data obtained from clinical records. Potential risk factors for detectable CMV viraemia (≥600 copies/ml) and all-cause mortality were assessed using univariable analysis and Cox Proportional Hazards Regression.ResultsThere were 438 transplants performed on 435 recipients. The following factors increased the risk of CMV viraemia with viral loads ≥600 copies/ml: Donor positive/Recipient negative status; receiving a graft from a deceased donor; and receiving a graft from a donor aged 60 years and over. CMV viraemia with viral loads ≥656 copies/ml was a risk factor for death following renal transplantation, as was being aged 65 years and above at transplant, being Aboriginal and having vascular disease. Importantly 37% of the episodes of CMV viraemia with viral loads ≥656 copies/ml occurred while the patients were expected to be on CMV prophylaxis.ConclusionsCMV viraemia (≥656 copies/ml) was associated with all-cause mortality in multivariable analysis, and CMV viraemia at ≥656 copies/ml commonly occurred during the period when renal transplant recipients were expected to be on antiviral prophylaxis. A greater vigilance in monitoring CMV levels if antiviral prophylaxis is stopped prematurely or poor patient compliance is suspected could protect some renal transplant recipients from adverse outcomes such as premature mortality.

BackgroundBK virus is a polyoma virus causing renal allograft nephropathy. Reduction of immunosuppression with the early recognition of significant BK viral loads in urine and plasma can effectively prevent BKV associated nephropathy (BKVN), however the optimal compartment and frequency of BK viral load measurement post renal transplantation are undetermined. Our purpose was to examine time to detection and viral loads in urine compared to plasma, and establish viral load cut-offs associated with histological BKVN.MethodsWe performed a retrospective analysis of the BKV screening frequency and compartment(s) of 277 adult renal transplant recipients (RTR).ResultsBKVN was histologically diagnosed in 17 (6.1 %) RTR. In cases where both urine and plasma were tested fortnightly for 6 months (n = 53), BKV was detected in the urine 29 days earlier than plasma. Fortnightly (n = 72) versus 3-monthly (n = 78) testing demonstrated that BKV was detected in the urine significantly earlier (median 63 versus 97 days, p = 0.001) and at a lower level (median 3.27 versus 6.71 log10 c/mL, p < 0.001) with more frequent testing, but this difference was not evident in plasma first detection (80 versus 95 days, p = 0.536) or first positive viral load (3.18 versus 3.30 log10 c/mL, p = 0.603). The optimum cut-off BK viral load for histological diagnosis of BKVN was 4.10 log10 c/mL for the first positive urine, 3.79 log10 c/mL for the first positive plasma, 9.24 log10 c/mL for the peak urine, and 4.53 log10 c/mL for the peak plasma.ConclusionsFrequent urinary BK viral load screening for the prevention of BKVN is suggested due to its high sensitivity and earlier detection.

Penicillium marneffei is a thermally dimorphic fungus that can cause severe opportunistic infections in endemic regions of Southeast Asia, particularly in individuals infected with human immunodeficiency virus-1, but has rarely been reported in solid organ transplant recipients. Herein, we report the first case, to our knowledge, of P. marneffei infection in a lung transplant recipient, occurring in a 41-year-old woman 28 months post lung transplantation, after recent travel to Vietnam. We have reviewed the literature to derive some management principles for this rare infection in this clinical context. The number of P. marneffei infections in transplant recipients may increase, as a result of increasing rates of transplantation and travel to endemic areas.

Background Invasive fungal infections (IFI) are common after lung transplantation with reported incidence of 8.1% to 16% at 12 months post‐transplant, and 3‐month all‐cause mortality after IFI of 21.7%. Methods We performed a retrospective study of IFI and fungal colonization in lung transplants (LTs) from November 2004 to February 2017. Results 137 LTs were followed for a median 4.1 years (IQR 2.1‐6.2 years). In addition to nebulized amphotericin for the transplant admission to all LTs, systemic mold‐active azole was given to 80/130 (61.5%) LTs in the first 6 months post‐transplant, 57/121 (47.1%) in the period 6‐12 months after transplant, and 93/124 (75%) in the period more than 12 months post‐transplant. Mold airways colonization was found in 81 (59.1%) LTs before and 110 (80.3%) LTs after transplantation. There were 13 IFIs for an overall incidence of 2.1 per 100 person‐years, occurring at a median 583 days (IQR 182‐1110 days) post‐transplant, a cumulative incidence of 3.8% at 1 year, 7.6% at 3 years and 10.1% at 5 years post‐transplant. All‐cause 3‐month mortality after IFI was 7.7%. Aspergillus species followed by Scedosporium apiospermum and Cryptococcus species were the commonest fungi causing IFI. Conclusions In our cohort the rate of IFI was comparatively low, likely because of comprehensive early antifungal use and preemptive therapy at any time after transplant. Prospective studies of fungal colonization late after LT are required to determine the risks and benefits of watchful waiting compared to preemptive therapy.

Patients with haematological malignancies, haemopoietic stem cell transplant recipients and patients requiring admission to intensive care settings are at high risk for invasive candidiasis (IC). Over the past decade, there has been increased reporting of nonalbicans species and fluconazole resistance in Australia. These guidelines provide updated evidence-based recommendations for the diagnosis and management of IC in adult and paediatric haematology, oncology and intensive care settings. Optimal pharmacological and non-pharmacological management are discussed. Recent studies strengthen the recommendation for an echinocandin agent as first-line therapy for high-risk patients with IC. Mortality benefit has also been demonstrated for nonpharmacological management, including removal of central venous catheters, infectious diseases consultation and use of care bundles. Healthcare facilities managing immunocompromised patient populations should therefore adopt implementation strategies for these multimodal interventions.

BackgroundPanton Valentine Leukocidin (PVL) has been associated with invasive Staphylococcus aureus soft tissue and pneumonic infections.MethodsFrom September 2007 to January 2009 at Royal Perth Hospital we tested for the PVL gene in S. aureus isolates from an invasive site, a suspected PVL-related soft tissue infection and all MRSA isolates. We could access medical records for 141 PVL positive (PVL + ve) infections and compared these to a control group comprised of 148 PVL negative (PVL-ve) infections.ResultsIn the PVL + ve group 62 isolates were MRSA (48 were ST93-MRSA-IV) and 79 isolates were methicillin-sensitive S. aureus, and in the PVL-ve group 56 were MRSA (50 were WA-MRSA strains) and 92 were methicillin-sensitive S. aureus. We found the presence of PVL to be significantly associated with younger age, aboriginality, intravenous drug use, community acquisition, shorter length of hospital stay and lower mortality at 1 year. Overall PVL + ve infections more often required surgical intervention (73.0% versus 44.6%, p < 0.001) and were less often polymicrobial (8.5% versus 41.2%, p < 0.001). PVL + ve isolates were more often susceptible to clindamycin (87.9% versus 73.0%, p = 0.002).ConclusionsThis study demonstrates that PVL + ve infections are associated with a distinct clinical picture, predominantly pyogenic skin and soft tissue infections often requiring surgery, disproportionately affecting patients who are younger, indigenous or with fewer health-care risk factors.

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