Early-life origins of disparities in chronic diseases among Indigenous youth: pathways to recovering health disparities from intergenerational trauma.

Indigenous women and children experience some of the most profound health disparities globally. These disparities are grounded in historical and contemporary trauma secondary to colonial atrocities perpetuated by settler society. The health disparities that exist for chronic diseases may have their origins in early-life exposures that Indigenous women and children face. Mechanistically, there is evidence that these adverse exposures epigenetically modify genes associated with cardiometabolic disease risk. Interventions designed to support a resilient pregnancy and first 1000 days of life should abrogate disparities in early-life socioeconomic status. Breastfeeding, prenatal care and early child education are key targets for governments and health care providers to start addressing current health disparities in cardiometabolic diseases among Indigenous youth. Programmes grounded in cultural safety and co-developed with communities have successfully reduced health disparities. More works of this kind are needed to reduce inequities in cardiometabolic diseases among Indigenous women and children worldwide.

Screening for Zika virus in deceased organ donors in Florida.

Zika virus (ZIKV) cases have been detected across the United States (US) and locally acquired cases have been reported in Florida. Currently, there are no ZIKV screening guidelines and no data on the incidence among organ donors in the US. This retrospective study was conducted at Jackson Memorial-Miami Transplant Institute. Positive ZIKV tests in local deceased organ donors were investigated from 6/2016 to 1/2017. We evaluated demographics and risk factors for ZIKV infection among organ donors and transplant outcomes among recipients of donors with positive ZIKV testing. One hundred forty-two donors were analyzed. Ten percent had traveled to ZIKV-endemic countries and 19% had outdoor occupations. Only 3% had positive ZIKV IGG. None had a positive ZIKV IGM or PCR. ZIKV-positive donors were more likely to have traveled to ZIKV-endemic countries (50% vs. 9%, P = .05). The kidneys from a ZIKV-positive donor were transplanted in our hospital with no 6-month rejection, graft failure, or death in the recipients. Our study demonstrated a low prevalence of ZIKV among deceased donors in our community. Despite local ZIKV transmission, ZIKV was more common in donors who traveled to ZIKV-endemic countries. This cohort demonstrated excellent outcomes in recipients of ZIKV IGG-positive donors. However, larger studies are needed.

Syndrome of Inappropriate Anti-Diuretic Hormone Secretion Secondary to Strongyloides stercoralis Infection in an Allogeneic Stem Cell Transplant Patient: A Case Report and Literature Review.

Syndrome of inappropriate anti-diuretic hormone (SIADH) has been reported to be associated with systemic Strongyloides stercoralis. Here, we report a case of a stem cell transplant (SCT) recipient who developed severe SIADH secondary to systemic S Stercoralis. The SIADH resolved quickly after treating the systemic S Stercoralis with ivermectin. A systematic review of the literature was performed by PubMed, Scopus, and Cochrane database search. Only eight cases of S Stercoralis in allogeneic SCT recipients have been previously reported. To our knowledge, ours is the first reported case of SIADH secondary to S Stercoralis infection in an allogeneic SCT recipient. Prior to transplantation, even if asymptomatic, patients from endemic regions should be screened with strongyloides immunoglobulin (Ig)G serology. Pretransplantation eosinophilia should be evaluated by screening multiple stool samples for ova and parasites. Transplant candidates with positive serology or stool tests can be treated pretransplantation to eradicate infection. Patients at risk for S Stercoralis who develop nonspecific gastrointestinal complaints, rash, pulmonary infiltrates, or gram-negative bacteremia or meningitis may have S Stercoralis hyperinfection syndrome. Our case indicates that the development of SIADH may be an additional clue to this diagnosis. Appropriate diagnostic studies, including repeat stool and other body fluid sampling, should be expedited and ivermectin therapy initiated rapidly to prevent significant morbidity and mortality.

Pretransplant CD4 Count Influences Immune Reconstitution and Risk of Infectious Complications in Human Immunodeficiency Virus-Infected Kidney Allograft Recipients.

In current practice, human immunodeficiency virus-infected (HIV(+) ) candidates with CD4 >200 cells/mm(3) are eligible for kidney transplantation; however, the optimal pretransplant CD4 count above this threshold remains to be defined. We evaluated clinical outcomes in patients with baseline CD4 >350 and <350 cells/mm(3) among 38 anti-thymocyte globulin (ATG)-treated HIV-negative to HIV(+) kidney transplants performed at our center between 2006 and 2013. Median follow-up was 2.6 years. Rates of acute rejection and patient and graft survival were not different between groups. Occurrence of severe CD4 lymphopenia (<200 cells/mm(3) ), however, was more common among patients with a baseline CD4 count 200-349 cells/mm(3) compared with those transplanted at higher counts (75% vs. 30% at 4 weeks [p = 0.04] and 71% vs. 5% at 52 weeks [p = 0.001], respectively, after transplant). After adjusting for age, baseline CD4 count of 200-349 cells/mm(3) was an independent predictor of severe CD4 lymphopenia at 4 weeks (relative risk [RR] 2.6; 95% confidence interval [CI] 1.3-5.1) and 52 weeks (RR 14.3; 95% CI 2-100.4) after transplant. Patients with CD4 <200 cells/mm(3) at 4 weeks had higher probability of serious infections during first 6 months after transplant (19% vs. 50%; log-rank p = 0.05). These findings suggest that ATG must be used with caution in HIV(+) kidney allograft recipients with a pretransplant CD4 count <350 cells/mm(3) .

Demographics and prevalence of positive QuantiFERON-TB Gold In-Tube test in renal transplant candidates.

BACKGROUND: Latent tuberculosis infection (LTBI) screening prior to solid organ transplantation is standard of care. QuantiFERON-TB Gold In-Tube (QFT-GIT) test is the preferred diagnostic test for renal transplant candidates (RTC). QFT-GIT reversions and the potential delay of living-donor kidney transplantation (LDKT) because of QFT-GIT positivity have not been examined previously in RTC. METHODS: We evaluated the prevalence of positive QFT-GIT in RTC from January 1 through December 31, 2011. In addition, we examined the demographic and renal disease data differences between QFT-GIT-positive and -negative patients, changes in QFT-GIT results, and positive QFT-GIT results reverting to negative. Lastly, we evaluated if QFT-GIT-positive patients were less likely to undergo LDKT within 6 months of QFT-GIT testing. RESULTS: In total, 722 RTC were analyzed, 16% of whom had positive QFT-GIT. The QFT-GIT-positive patients were more likely to be older and foreign-born, P < 0.0001. Haitians had the highest prevalence. Of the 119 QFT-GIT-positive patients, 25% had low/intermediate-positive results and were more likely to revert to negative, compared with patients with high-positive QFT-GIT results (50% vs. 0%, P = 0.01). A trend was seen toward fewer QFT-GIT-positive patients undergoing LDKT, compared with QFT-GIT-negative patients (0% vs. 3%, P = 0.09). CONCLUSIONS: Our high prevalence was likely a result of the high number of foreign-born RTC. Half of our small subset of low/intermediate-positive QFT-GIT patients reverted to negative. QFT-GIT-positive patients were more likely to have their LDKT delayed.

Solid organ transplantation from hepatitis B virus-positive donors: consensus guidelines for recipient management.

Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non-liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti-HBc+) donors. Organs from anti-HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non-liver recipients but is not recommended in immune non-liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost-effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended.

Randomized, double-blind trial of anidulafungin versus fluconazole for prophylaxis of invasive fungal infections in high-risk liver transplant recipients.

Invasive fungal infections (IFIs) are a common complication in liver transplant recipients. There are no previous randomized trials of an echinocandin for the prevention of IFIs in solid organ transplant recipients. In a randomized, double-blind trial conducted at University-affiliated transplant centers, 200 high-risk liver transplant recipients (100 patients per group) received either anidulafungin or fluconazole for antifungal prophylaxis. Randomization was stratified by Model for End-Stage Liver Disease score ≥30 and receipt of a pretransplant antifungal agent. The primary end point was IFI in a modified intent-to-treat analysis. The overall incidence of IFI was similar for the anidulafungin (5.1%) and the fluconazole groups (8.0%) (OR 0.61, 95% CI 0.19-1.94, p = 0.40). However, anidulafungin prophylaxis was associated with less Aspergillus colonization or infection (3% vs. 9%, p = 0.08), lower breakthrough IFIs among patients who had received pretransplant fluconazole (0% vs. 27%, p = 0.07), and fewer cases of antifungal resistance (no cases vs. 5 cases). Both drugs were well-tolerated. Graft rejection, fungal-free survival, and mortality were similar for both groups. Thus, anidulafungin and fluconazole have similar efficacy for antifungal prophylaxis in most liver transplant recipients. Anidulafungin may be beneficial if the patient has an increased risk for Aspergillus infection or received fluconazole before transplantation.

Considerations for screening live kidney donors for endemic infections: a viewpoint on the UNOS policy.

In February 2013, the Organ Procurement and Transplantation Network mandated that transplant centers perform screening of living kidney donors prior to transplantation for Strongyloides, Trypanosoma cruzi and West Nile virus (WNV) infection if the donor is from an endemic area. However, specific guidelines for screening were not provided, such as the optimal testing modalities, timing of screening prior to donation and the appropriate selection of donors. In this regard, the American Society of Transplantation Infectious Diseases Community of Practice, together with disease-specific experts, has developed this viewpoint document to provide guidance for the testing of live donors for Strongyloides, T. cruzi and WNV infection, specifically identifying at-risk populations and testing algorithms, including advantages, limitations and interpretation of results.

Fatal herpes simplex virus type 2 hepatitis in a heart transplant recipient: a case report and review of the literature.

Herpes simplex virus (HSV) hepatitis is often unrecognized clinically with most untreated cases diagnosed postmortem. HSV hepatitis has been reported in solid organ transplant (SOT) recipients, mostly in kidney and liver transplants, and rarely in heart transplant recipients. We describe a fatal case of community-acquired HSV-2 hepatitis in a 24-year-old heart transplant recipient occurring 3 years after transplant. We also review the literature summarizing HSV hepatitis and the potential role of quantitative HSV polymerase chain reaction monitoring in the SOT population.

Diagnosis and management of tuberculosis in transplant donors: a donor-derived infections consensus conference report.

Mycobacterium tuberculosis is a ubiquitous organism that infects one-third of the world's population. In previous decades, access to organ transplantation was restricted to academic medical centers in more developed, low tuberculosis (TB) incidence countries. Globalization, changing immigration patterns, and the expansion of sophisticated medical procedures to medium and high TB incidence countries have made tuberculosis an increasingly important posttransplant infectious disease. Tuberculosis is now one of the most common bacterial causes of solid-organ transplant donor-derived infection reported in transplant recipients in the United States. Recognition of latent or undiagnosed active TB in the potential organ donor is critical to prevent emergence of disease in the recipient posttransplant. Donor-derived tuberculosis after transplantation is associated with significant morbidity and mortality, which can best be prevented through careful screening and targeted treatment. To address this growing challenge and provide recommendations, an expert international working group was assembled including specialists in transplant infectious diseases, transplant surgery, organ procurement and TB epidemiology, diagnostics and management. This working group reviewed the currently available data to formulate consensus recommendations for screening and management of TB in organ donors.

Donor-derived fungal infections in organ transplant recipients: guidelines of the American Society of Transplantation, infectious diseases community of practice.

Donor-derived fungal infections can be associated with serious complications in transplant recipients. Most cases of donor-derived candidiasis have occurred in kidney transplant recipients in whom contaminated preservation fluid is a commonly proposed source. Donors with cryptococcal disease, including those with unrecognized cryptococcal meningoencephalitis may transmit the infection with the allograft. Active histoplasmosis or undiagnosed and presumably asymptomatic infection in the donor that had not resolved by the time of death can result in donor-derived histoplasmosis in the recipient. Potential donors from an endemic area with either active or occult infection can also transmit coccidioidomycosis. Rare instances of aspergillosis and other mycoses, including agents of mucormycosis may also be transmitted from infected donors. Appropriate diagnostic evaluation and prompt initiation of appropriate antifungal therapy are warranted if donor-derived fungal infections are a consideration. This document discusses the characteristics, evaluation and approach to the management of donor-derived fungal infections in organ transplant recipients.

Screening and treatment of chagas disease in organ transplant recipients in the United States: recommendations from the chagas in transplant working group.

Donor-derived transmission of Trypanosoma cruzi, the etiologic agent of Chagas disease, has emerged as an issue in the United States over the past 10 years. Acute T. cruzi infection causes substantial morbidity and mortality in the posttransplant setting if not recognized and treated early. We assembled a working group of transplant infectious disease specialists, laboratory medicine specialists, organ procurement organization representatives and epidemiologists with expertise in Chagas disease. Based on review of published and unpublished data, the working group prepared evidence-based recommendations for donor screening, and follow-up testing and treatment of recipients of organs from infected donors. We advise targeted T. cruzi screening of potential donors born in Mexico, Central America and South America. Programs can consider transplantation of kidneys and livers from T. cruzi-infected donors with informed consent from recipients. However, we recommend against heart transplantation from infected donors. For other organs, we recommend caution based on the anticipated degree of immunosuppression. Our recommendations stress the need for systematic monitoring of recipients by polymerase chain reaction, and microscopy of buffy coat and advance planning for immediate antitrypanosomal treatment if recipient infection is detected. Data on management and outcomes of all cases should be collected to inform future guidelines and to assist in coordination with public health authorities.

Pulmonary imaging of pandemic influenza H1N1 infection: relationship between clinical presentation and disease burden on chest radiography and CT.

The potential for pulmonary involvement among patients presenting with novel swine-origin influenza A (H1N1) is high. To investigate the utility of chest imaging in this setting, we correlated clinical presentation with chest radiographic and CT findings in patients with proven H1N1 cases. Subjects included all patients presenting with laboratory-confirmed H1N1 between 1 May and 10 September 2009 to one of three urban hospitals. Clinical information was gathered retrospectively, including symptoms, possible risk factors, treatment and hospital survival. Imaging studies were re-read for study purposes, and CXR findings compared with CT scans when available. During the study period, 157 patients presented with subsequently proven H1N1 infection. Hospital admission was necessary for 94 (60%) patients, 16 (10%) were admitted to intensive care and 6 (4%) died. An initial CXR, carried out for 123 (78%) patients, was abnormal in only 40 (33%) cases. Factors associated with increased likelihood for radiographic lung abnormalities were dyspnoea (p<0.001), hypoxaemia (p<0.001) and diabetes mellitus (p = 0.023). Chest CT was performed in 21 patients, and 19 (90%) showed consolidation, ground-glass opacity, nodules or a combination of these findings. 4 of 21 patients had negative CXR and positive CT. Compared with CT, plain CXR was less sensitive in detecting H1N1 pulmonary disease among immunocompromised hosts than in other patients (p = 0.0072). A normal CXR is common among patients presenting to the hospital for H1N1-related symptoms without evidence of respiratory difficulties. The CXR may significantly underestimate lung involvement in the setting of immunosuppression.

Guidance on novel influenza A/H1N1 in solid organ transplant recipients.

Novel influenza A/H1N1 virus has caused significant illness worldwide. In response to this global crisis, the American Society of Transplantation (AST) Infectious Diseases Community of Practice and the Transplant Infectious Diseases section of The Transplantation Society (TTS) developed a guidance document for novel H1N1. In this paper, we discuss current guidance for H1N1 as it relates to solid organ transplantation. We include discussion around clinical presentation, diagnosis, therapy and prevention specifically addressing areas such as chemoprophylaxis, immunization and donor-derived infection. Although this document addresses conditions specific to novel H1N1, many principles could be applied to future pandemics. As new information emerges about novel H1N1, updates will be made to the electronic version of the document posted on the websites of the AST and TTS.

Factors related to survival and treatment success in invasive candidiasis or candidemia: a pooled analysis of two large, prospective, micafungin trials.

Crude and attributable mortality rates in patients with candidemia and invasive candidiasis remain unacceptably high. It is important to reach a more complete understanding of the risk factors underlying poor outcomes in patients with invasive Candida infections. Micafungin therapy has been assessed in two phase 3 trials compared to either liposomal amphotericin B or caspofungin. The availability of this large dataset allows the analyses of non-drug factors associated with survival and treatment success. A multivariate regression analysis was performed on data from the two trials separately and as a pooled analysis (N = 1,070). Analysis outcomes were survival at 42 days post-initiation of therapy and treatment success. For the pooled analysis, treatment success was significantly more likely for candidemia than invasive candidiasis. Both survival and treatment success were significantly less likely for the non-removal of catheter versus removal, Asian-Indians versus Caucasians, APACHE II score >20 to 30 versus or=70 years versus <50 years, baseline corticosteroids, and persistent neutropenia. Survival was also significantly less likely for treatment in other regions versus North America and for patients with renal failure at baseline. These findings help to define non-antifungal drug factors that may impact survival and treatment success in invasive candidiasis or candidemia.

Mycobacterium abscessus infection in solid organ transplant recipients: report of three cases and review of the literature.

Mycobacterium abscessus is an ubiquitous organism found in the environment. This rapidly growing mycobacterium infrequently causes disease in humans; however, in immunocompromised hosts, disease can range from localized cutaneous lesions to disseminated infection. The organism is resistant to most antimycobacterial drugs and therapy can be limited by drug interactions. The exact incidence of M. abscessus infection among solid organ transplant (SOT) recipients is unknown; data are only available from previously reported cases in the literature. We describe 3 cases of M. abscessus infection in SOT recipients diagnosed within a 5-month period. One of the cases followed multi-visceral transplantation, the first such case to be reported in the literature. An epidemiological investigation did not reveal significant commonalities among the cases, and pulsed-field gel electrophoresis of genomic DNA of the case isolates confirmed their non-identity. All cases improved with antibiotic therapy, most notably with the new glycylcycline, tigecycline, along with surgical intervention in 2 of the cases. In addition, we review features and characteristics of M. abscessus infections in recipients of SOT reported in the literature from 1992 to 2008 and summarize some selected therapeutic concerns and issues related to treatment.

A case of subcutaneous Mycoleptodiscus indicus infection in a liver transplant recipient successfully treated with antifungal therapy.

Mycoleptodiscus indicus, a dematiaceous mold, occurs on the leaves of a number of different host plants and has been only recently described as a cause of human infection. Immunosuppressed individuals are at risk for developing infections with opportunistic fungal pathogens, which are a major cause of morbidity and mortality in this population. In addition, the treatment of infections caused by these fungi is frequently challenging. We report a case of M. indicus subcutaneous infection in a 51-year-old man with human immunodeficiency virus and hepatitis C co-infection, who had a liver transplant. He developed skin nodules with a sporotrichoid lymphangitic distribution. Histopathology demonstrated unusual fungal elements with angioinvasion. Mycology cultures isolated a dematiaceous mold with the characteristic curved hyaline conidia of M. indicus. Initial treatment involved a combination of amphotericin B lipid complex and voriconazole, followed by monotherapy with voriconazole. The subcutaneous lesions resolved completely after 4 months of antifungal therapy.

Hepatic gas gangrene following orthotopic liver transplantation: three cases treated with re-transplantation and a review of the literature.

Gas gangrene is a rare and devastating infectious process that can occur after liver transplantation, most often following hepatic artery thrombosis. We here report 3 cases of gas gangrene following orthotopic liver transplantation. Blood cultures were positive for Clostridium clostridiiforme in one case. In 2 other cases liver tissue from explanted specimens was positive for Enterobacter cloacae. Ultrasound demonstrated hepatic artery thrombosis and computed tomography imaging revealed diffuse liver necrosis with gas formation in each case. All 3 patients were successfully treated with a combination of antibiotics and emergent re-transplantation. We review previously published cases of gas gangrene after liver transplant and emphasize the importance of hepatic artery thrombosis in the development of this syndrome as well as the frequent involvement of non-clostridial organisms. Early diagnosis and aggressive combined medical and surgical treatment including re-transplantation are essential for successful treatment of these rare and catastrophic infections.

Ophiopogon root (Radix Ophiopogonis) prevents ultra-structural damage by SO2 in an epithelial injury model for studies of mucociliary transport.

We studied the action of the herb, Ophiopogon root (OR) in a epithelial injury model, hypothesizing that it may have beneficial effects on mucociliary transport following injury to the palate induced by sodium metabisulphite (MB) which releases SO(2) on contact with water. OR (extract from 1g of root/ml)-incubated palates and non-incubated palates were compared to assess the effect of MB on mucociliary clearance on the bull frog palate. MB 10(-1) M, acutely increased mucociliary clearance time (MCT) by 254.5 +/- 57.3% in untreated and 243.3 +/- 98.5% in OR-incubated palates, (over all significance assessed by one-way ANOVA, F = 12.82, p < 0.001, df = 8,54 for MB and F = 10.56, p < 0.001, df = 8,54 for OR). MCT returned to normal during recovery in OR-treated palates following MB. In untreated palates, MCT did not return to control values during a similar recovery period. ANOVA comparing MCTs in the recovery period in untreated vs OR-treated palates was significantly different (F = 2.92, p < 0.03, df = 5,36). SEM images of epithelial tissue, analyzed by morphometry, showed a 25 +/- 12% loss of ciliated cells in untreated palates and little or no damage to cilia in OR-treated palates. Intact groups of ciliated cells were found in SEM micrographs of mucus from MB-treated palates. We conclude that the loss of cilia or ciliated cells prevented full recovery of MCT after MB in untreated palates. In OR-incubated palates, mucociliary transport was completely restored within 20 min after topical application of MB, possibly through a protective action on the extra-cellular matrix.