Transplant of organs from donors with positive SARS-CoV-2 nucleic acid testing: A report from the organ procurement and transplantation network ad hoc disease transmission advisory committee.

BACKGROUND: Decisions to transplant organs from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test-positive (NAT+) donors must balance risk of donor-derived transmission events (DDTE) with the scarcity of available organs. METHODS: Organ Procurement and Transplantation Network (OPTN) data were used to compare organ utilization and recipient outcomes between SARS-CoV-2 NAT+ and NAT- donors. NAT+ was defined by either a positive upper or lower respiratory tract (LRT) sample within 21 days of procurement. Potential DDTE were adjudicated by OPTN Disease Transmission Advisory Committee. RESULTS: From May 27, 2021 (date of OTPN policy for required LRT testing of lung donors) to January 31, 2022, organs were recovered from 617 NAT+ donors from all OPTN regions and 53 of 57 (93%) organ procurement organizations. NAT+ donors were younger and had higher organ quality scores for kidney and liver. Organ utilization was lower for NAT+ donors compared to NAT- donors. A total of 1241 organs (776 kidneys, 316 livers, 106 hearts, 22 lungs, and 21 other) were transplanted from 514 NAT+ donors compared to 21 946 organs from 8853 NAT- donors. Medical urgency was lower for recipients of NAT+ liver and heart transplants. The median waitlist time was longer for liver recipients of NAT+ donors. The match run sequence number for final acceptor was higher for NAT+ donors for all organ types. Outcomes for hospital length of stay, 30-day mortality, and 30-day graft loss were similar for all organ types. No SARS-CoV-2 DDTE occurred in this interval. CONCLUSIONS: Transplantation of SARS-CoV-2 NAT+ donor organs appears safe for short-term outcomes of death and graft loss and ameliorates the organ shortage. Further study is required to assure comparable longer term outcomes.

Updated U.S. Public Health Service Guideline for Testing of Transplant Candidates Aged <12 Years for Infection with HIV, Hepatitis B Virus, and Hepatitis C Virus - United States, 2022.

The U.S. Public Health Service (PHS) has periodically published recommendations about reducing the risk for transmission of HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) through solid organ transplantation (1-4). Updated guidance published in 2020 included the recommendation that all transplant candidates receive HIV, HBV, and HCV testing during hospital admission for transplant surgery to more accurately assess their pretransplant infection status and to better identify donor transmitted infection (4). In 2021, CDC was notified that this recommendation might be unnecessary for pediatric organ transplant candidates because of the low likelihood of infection after the perinatal period and out of concern that the volume of blood drawn for testing could negatively affect critically ill children.* CDC and other partners reviewed surveillance data from CDC on estimates of HIV, HBV, and HCV infection rates in the United States and data from the Organ Procurement & Transplantation Network (OPTN)† on age and weight distributions among U.S. transplant recipients. Feedback from the transplant community was also solicited to understand the impact of changes to the existing policy on organ transplantation. The 2020 PHS guideline was accordingly updated to specify that solid organ transplant candidates aged <12 years at the time of transplantation who have received postnatal infectious disease testing are exempt from the recommendation for HIV, HBV, and HCV testing during hospital admission for transplantation.

Assessing Solid Organ Donors and Monitoring Transplant Recipients for Human Immunodeficiency Virus, Hepatitis B Virus, and Hepatitis C Virus Infection - U.S. Public Health Service Guideline, 2020.

The recommendations in this report supersede the U.S Public Health Service (PHS) guideline recommendations for reducing transmission of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) through organ transplantation (Seem DL, Lee I, Umscheid CA, Kuehnert MJ. PHS guideline for reducing human immunodeficiency virus, hepatitis B virus, and hepatitis C virus transmission through organ transplantation. Public Health Rep 2013;128:247-343), hereafter referred to as the 2013 PHS guideline. PHS evaluated and revised the 2013 PHS guideline because of several advances in solid organ transplantation, including universal implementation of nucleic acid testing of solid organ donors for HIV, HBV, and HCV; improved understanding of risk factors for undetected organ donor infection with these viruses; and the availability of highly effective treatments for infection with these viruses. PHS solicited feedback from its relevant agencies, subject-matter experts, additional stakeholders, and the public to develop revised guideline recommendations for identification of risk factors for these infections among solid organ donors, implementation of laboratory screening of solid organ donors, and monitoring of solid organ transplant recipients. Recommendations that have changed since the 2013 PHS guideline include updated criteria for identifying donors at risk for undetected donor HIV, HBV, or HCV infection; the removal of any specific term to characterize donors with HIV, HBV, or HCV infection risk factors; universal organ donor HIV, HBV, and HCV nucleic acid testing; and universal posttransplant monitoring of transplant recipients for HIV, HBV, and HCV infections. The recommendations are to be used by organ procurement organization and transplant programs and are intended to apply only to solid organ donors and recipients and not to donors or recipients of other medical products of human origin (e.g., blood products, tissues, corneas, and breast milk). The recommendations pertain to transplantation of solid organs procured from donors without laboratory evidence of HIV, HBV, or HCV infection. Additional considerations when transplanting solid organs procured from donors with laboratory evidence of HCV infection are included but are not required to be incorporated into Organ Procurement and Transplantation Network policy. Transplant centers that transplant organs from HCV-positive donors should develop protocols for obtaining informed consent, testing and treating recipients for HCV, ensuring reimbursement, and reporting new infections to public health authorities.

Cytomegalovirus myocarditis in solid organ transplant recipients: A case series and review of literature.

Cytomegalovirus (CMV) is a DNA virus of the Herpesviridae family and is estimated to affect 15%-30% of high-risk solid organ transplant recipients. Typical manifestations of CMV end-organ disease in this population include colitis, esophagitis, and pneumonitis, and myocarditis is a rarely reported manifestation. We describe two cases of CMV myocarditis in solid organ transplant recipients and review the literature regarding previously published cases of CMV myocarditis.

Impact of US Public Health Service increased risk deceased donor designation on organ utilization.

Under US Public Health Service guidelines, organ donors with risk factors for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) are categorized as increased risk donors (IRD). Previous studies have suggested that IRD organs are utilized at lower rates than organs from standard risk donors (SRD), but these studies were conducted prior to universal donor nucleic acid test screening. We conducted risk-adjusted analyses to determine the effect of IRD designation on organ utilization using 2010-2017 data (21 626 heart, 101 160 kidney, 52 714 liver, and 16 219 lung recipients in the United States) from the Organ Procurement and Transplantation Network. There was no significant difference (P < .05) between risk-adjusted utilization rates for IRD vs SRD organs for adult hearts and livers and pediatric kidneys, livers, and lungs. Significantly lower utilization was found among IRD adult kidneys, lungs, and pediatric hearts. Analysis of the proportion of transplanted organs recovered from IRD by facility suggests that a subset of facilities contribute to the underutilization of adult IRD kidneys. Along with revised criteria and nomenclature to identify donors with HIV, HBV, or HCV risk factors, educational efforts to standardize informed consent discussions might improve organ utilization.

Characteristics of Deceased Solid Organ Donors and Screening Results for Hepatitis B, C, and Human Immunodeficiency Viruses - United States, 2010-2017.

The ongoing U.S. opioid crisis has resulted in an increase in drug overdose deaths and acute hepatitis C virus (HCV) infections, with young persons (who might be eligible organ donors) most affected.*,† In 2013, the Public Health Service released a revised guideline to reduce the risk for unintended organ transplantation-associated hepatitis B virus (HBV), HCV, and human immunodeficiency virus (HIV) transmission (1). The guideline describes criteria to categorize donors at increased risk (increased risk donors [IRDs]) for transmitting these viruses to recipients (1). It also recommends universal donor testing for HBV, HCV, and HIV.§ CDC analyzed deceased donor data for the period 2010-2017 reported to the Organ Procurement and Transplantation Network for IRDs and standard risk donors (SRDs) (i.e., donors who do not meet any of the criteria for increased risk designation). During this period, the proportion of IRDs increased approximately 200%, from 8.9% to 26.3%; the percentage with drug intoxication reported as the mechanism of death also increased approximately 200%, from 4.3% to 13.4%; and the proportion of these donors with reported injection drug use (IDU) increased approximately 500%, from 1.3% to 8.0%. Compared with SRDs, IRDs were significantly more likely to have positive HBV and HCV screening results. These findings demonstrate the continuing need for identifying viral bloodborne pathogen infection risk factors among deceased donors to reduce the risk for transmission, monitor posttransplant infection in recipients, and offer treatment if infection occurs.

Marijuana use in transplantation: A call for clarity.

Transplant centers have varying policies for marijuana (MJ) use in donors, transplant candidates, and recipients. Rationales for these differences range from concerns for fungal complications, impaired adherence, and drug interactions. This paper reviews the current status of MJ policies and practices in transplant centers and results of a survey sent to the American Society of Transplantation (AST) membership by the Executive Committee of the AST Infectious Diseases Community of Practice.The purpose of the survey was to compare policies and concerns of MJ use to actual observed complications. Of the 3321 surveys sent, 225 members (8%) responded. Transplant centers varied in their approval processes, differing even in organ types within the same institutions. Furthermore, there was discordance among transplant centers in their perceived risks of marijuana use as opposed to complications actually observed. An increasing number of states continue to legalize medical and recreational MJ resulting in widespread availability. Further research is needed to assess the validity of concerns for complications of MJ use in potential donors and recipients. Ultimately, standardized guidelines should be established based on studies and evidence-based criteria to assist transplant programs in their policies around the use of cannabis in their donors and recipients.

Zika virus: a cause of concern in transplantation?

PURPOSE OF REVIEW: Worldwide, the number of countries reporting Zika virus (ZKV) infection continues to increase. Although 80% of cases are asymptomatic, ZKV has been identified as a neurotropic virus associated with congenital microcephaly, Guillain-Barre' syndrome, and meningoencephalitis. Until recently, infection in transplant recipients has not been identified. This study will review the existing literature on ZKV infection, laboratory testing, and management in transplant recipients. RECENT FINDINGS: Donor-derived transfusion of contaminated blood products and naturally occurring ZKV infections have been recently reported in solid organ and stem cell transplant recipients, ranging from asymptomatic infections to meningoencephalitis. Interpretation of diagnostic testing of ZKV is evolving, with prolonged viral shedding identified in blood, semen, and urine of unclear significance. Serologic testing may be associated with cross-reactivity with other flaviviridae, requiring plaque reduction neutralization testing for confirmation. Thus far, donor screening guidelines for transplantation have not been established. SUMMARY: The study reviews the limited existing literature in transplant recipients infected with ZKV, available laboratory testing and management. Ultimately, guidelines are needed for donor screening from high-risk areas, interpretation of studies and management of infected patients to ensure safe transplantation.

Assessment of cytomegalovirus-specific cell-mediated immunity for the prediction of cytomegalovirus disease in high-risk solid-organ transplant recipients: a multicenter cohort study.

BACKGROUND: Cytomegalovirus (CMV) disease remains an important problem in solid-organ transplant recipients, with the greatest risk among donor CMV-seropositive, recipient-seronegative (D(+)/R(-)) patients. CMV-specific cell-mediated immunity may be able to predict which patients will develop CMV disease. METHODS: We prospectively included D(+)/R(-) patients who received antiviral prophylaxis. We used the Quantiferon-CMV assay to measure interferon-γ levels following in vitro stimulation with CMV antigens. The test was performed at the end of prophylaxis and 1 and 2 months later. The primary outcome was the incidence of CMV disease at 12 months after transplant. We calculated positive and negative predictive values of the assay for protection from CMV disease. RESULTS: Overall, 28 of 127 (22%) patients developed CMV disease. Of 124 evaluable patients, 31 (25%) had a positive result, 81 (65.3%) had a negative result, and 12 (9.7%) had an indeterminate result (negative mitogen and CMV antigen) with the Quantiferon-CMV assay. At 12 months, patients with a positive result had a subsequent lower incidence of CMV disease than patients with a negative and an indeterminate result (6.4% vs 22.2% vs 58.3%, respectively; P < .001). Positive and negative predictive values of the assay for protection from CMV disease were 0.90 (95% confidence interval [CI], .74-.98) and 0.27 (95% CI, .18-.37), respectively. CONCLUSIONS: This assay may be useful to predict if patients are at low, intermediate, or high risk for the development of subsequent CMV disease after prophylaxis. CLINICAL TRIALS REGISTRATION: NCT00817908.

The variable presentations and broadening geographic distribution of hepatic fascioliasis.

We report 2 unrelated cases of hepatic fascioliasis in travelers returning to the United States from Africa and the Middle East. The first case presented with acute infection. Prominent clinical features included abdominal pain, elevated liver transaminases, serpiginous hepatic lesions, pericapsular hematoma, and marked peripheral eosinophilia. The second case was diagnosed in the chronic stage of infection and presented with right upper quadrant abdominal pain, cystic hepatic lesions, and an adult fluke in the common bile duct. We review the life cycle of Fasciola species, the corresponding clinical features during the stages of human infection, diagnostic methods, and the evolving understanding of the epidemiology of human fascioliasis, particularly emphasizing fascioliasis in African countries.

Risk of Severe Acute Respiratory Syndrome Coronavirus 2 Transmission Through Solid Organ Transplantation and Outcomes of Coronavirus Disease 2019 Among Recent Transplant Recipients.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmissible through lung transplantation, and outcomes among infected organ recipients may be severe. Transmission risk to extrapulmonary organ recipients and recent (within 30 days of transplantation) SARS-CoV-2-infected recipient outcomes are unclear. Methods: During March 2020-March 2021, potential SARS-CoV-2 transmissions through solid organ transplantation were investigated. Assessments included SARS-CoV-2 testing, medical record review, determination of likely transmission route, and recent recipient outcomes. Results: During March 2020-March 2021, approximately 42 740 organs were transplanted in the United States. Forty donors, who donated 140 organs to 125 recipients, were investigated. Nine (23%) donors and 25 (20%) recipients were SARS-CoV-2 positive by nucleic acid amplification test (NAAT). Most (22/25 [88%]) SARS-CoV-2-infected recipients had healthcare or community exposures. Nine SARS-CoV-2-infected donors donated 21 organs to 19 recipients. Of these, 3 lung recipients acquired SARS-CoV-2 infections from donors with negative SARS-CoV-2 testing of pretransplant upper respiratory tract specimens but from whom posttransplant lower respiratory tract (LRT) specimens were SARS-CoV-2 positive. Sixteen recipients of extrapulmonary organs from SARS-CoV-2-infected donors had no evidence of posttransplant COVID-19. All-cause mortality within 45 days after transplantation was 6-fold higher among SARS-CoV-2-infected recipients (9/25 [36%]) than those without (6/100 [6%]). Conclusions: Transplant-transmission of SARS-CoV-2 is uncommon. Pretransplant NAAT of lung donor LRT specimens may prevent transmission of SARS-CoV-2 through transplantation. Extrapulmonary organs from SARS-CoV-2-infected donors may be safely usable, although further study is needed. Reducing recent recipient exposures to SARS-CoV-2 should remain a focus of prevention.

Impact of rituximab-associated B-cell defects on West Nile virus meningoencephalitis in solid organ transplant recipients.

Evidence suggests that West Nile virus (WNV) neuroinvasive disease occurs more frequently in both solid organ and human stem cell transplant recipients. The effect of concomitant anti-B-cell therapy with rituximab, a CD20(+) monoclonal antibody, on WNV infection in this population, however, has not been reported. We describe a case of a patient with alpha-1-antitrypsin deficiency who underwent single lung transplantation in 2005 and was maintained on tacrolimus, cytoxan and prednisone. More recently, she had received two courses of rituximab for recurrent A2-A3 grade rejection with concomitant capillaritis and presented six months later with rapid, fulminant WNV meningoencephalitis. Her diagnosis was made by cerebrospinal fluid (CSF) PCR but serum and CSF WNV IgM and IgG remained negative. She received WNV-specific hyperimmune globulin (Omr-Ig-Am) through a compassionate protocol. She experienced a rapidly progressive and devastating neurological course despite treatment and died three wk after onset of her symptoms. Autopsy revealed extensive meningoencephalomyelitis.

Left ventricular assist device outflow cannula obstruction by the rare environmental fungus Myceliophthora thermophila.

Left ventricular assist devices are used to provide mechanical circulatory support during end-stage heart failure either as a destination therapy or as a bridge to heart transplantation. Perioperative transesophageal echocardiography is becoming an invaluable tool to investigate device function during implantation and in case of mechanical malfunction. Most malfunctions are due to inflow graft occlusion, or device malfunction, while outflow graft dysfunction is rare. Here, we present a case of severe outflow conduit obstruction by a rare environmental fungus, Myceliophthora thermophila. After replacement of the infected device and intensive antifungal treatment, heart transplantation was performed 2 yr later.

Pharmacokinetic Drug-Drug Interactions Between Immunosuppressant and Anti-Infective Agents: Antimetabolites and Corticosteroids.

Infections account for 15-20% of deaths in transplant recipients, requiring rapid and appropriate therapeutic interventions. Many anti-infective agents interact with immunosuppressive regimens used in transplantation, placing patients at increased risk for adverse drug reactions and prolonged hospitalizations. There is established data regarding the level of evidence and magnitude of interactions between calcineurin inhibitors and mammalian target of rapamycin inhibitors with anti-infective agents. Less is known about the interactions with anti-proliferative agents and corticosteroids, with gaps in knowledge on the appropriate management of these interactions. The objective of this review was to highlight the pharmacokinetic drug-drug interactions between antimetabolites and corticosteroids with commonly used anti-infective agents.

Naturally acquired West Nile virus encephalomyelitis in transplant recipients: clinical, laboratory, diagnostic, and neuropathological features.

BACKGROUND: In the 2003 West Nile virus (WNV) epidemic, Colorado reported more WNV cases than any other state, including an unprecedented number in organ transplant recipients. METHODS: Physicians caring for transplant recipients hospitalized with naturally acquired WNV encephalitis provided data to characterize the clinical symptoms, results of diagnostic studies, and outcomes. RESULTS: Eleven transplant recipients were identified (4 kidney, 2 stem cell, 2 liver, 1 lung, and 2 kidney/pancreas). Seven were directly admitted to 1 of the 2 hospitals in the study, and 4 were referred to 1 of these centers from regional hospitals. All but 1 patient had a prodrome typical of WNV encephalitis in nonimmunosuppressed patients. Ten patients developed meningoencephalitis, which in 3 cases was associated with acute flaccid paralysis. One patient developed acute flaccid paralysis without encephalitis. Six patients had significant movement disorders including tremor, myoclonus, or parkinsonism. All patients had cerebrospinal fluid pleocytosis and WNV-specific IgM in the cerebrospinal fluid and/or serum. Cerebrospinal fluid cytologic studies (n = 5) showed atypical lymphocytes, some resembling plasma cells; however, flow cytometry (n = 3) showed that cells were almost exclusively of T-cell (not B-cell or plasma cell) lineage. Magnetic resonance images of the brain were abnormal in 7 of 8 tested patients, and electroencephalograms were abnormal in 7 of 7, with 2 showing periodic lateralized epileptiform discharges. Nine of 11 patients survived infection, but 3 had significant residual deficits. One patient died 17 days after admission, and autopsy findings revealed severe panencephalitic changes with multifocal areas of necrosis in the cerebral deep gray nuclei, brainstem, and spinal cord as well as diffuse macrophage influx in the periventricular white matter. A second patient died of complications of WNV encephalitis 6 months after hospital admission. CONCLUSIONS: Naturally acquired WNV encephalitis in transplant recipients shows diagnostic, clinical, and laboratory features similar to those reported in nonimmunocompromised individuals, but neuroimaging, electroencephalography, and autopsy results verify that these patients develop neurological damage at the severe end of the spectrum.

West Nile Virus Infection in the Immunocompromised Patient.

West Nile virus infection has become the predominant cause of flavivirus-associated encephalitis in the US. While 80 % of infected individuals are asymptomatic, 20 % develop symptoms including fever, headache, transient rash and gastrointestinal symptoms. Among the immunocompetent population, 1 in 150 develop neuroinvasive disease characterized by acute flaccid paralysis, Parkinsonian cogwheel rigidity, meningitis, encephalitis, meningoencephalitis and asymmetric muscle weakness (Mostashari et al. in Lancet 358:261-264, 2001). In the immunocompromised population such as transplant recipients and HIV-infected and chemotherapy patients, the incidence of neuroinvasive disease may be increased. The largest population studied is recipients of solid organ transplants, with data on both donor-derived and naturally occurring transmissions. The risk of neuroinvasive disease in donor-derived infection is estimated to be between 50 % and 75 % while in those with mosquito-borne transmission the risk is estimated at 40 % of those infected (Kumar et al. in Am J Transplant 4:1883-1888, 2004). With significant morbidity associated with donor transmission, specific pretransplant screening recommendations are reviewed. Treatment includes supportive care and consideration for the use of intravenous immunoglobulin.

Successful treatment of acyclovir-resistant herpes simplex virus type 2 proctitis with leflunomide in an HIV-infected man.

Human herpes simplex virus infections are very common and represent significant morbidity in the immunocompromised host. Patients with acyclovir resistant strains of HSV based on viral thymidine kinase gene mutations need alternative therapeutic approaches. Leflunomide has been shown to possess antiviral activity against several viruses. Herein we describe a case of acyclovir resistant HSV-2 proctitis in an HIV patient successfully treated with leflunomide without significant side effects.

Oral infections and antibiotic therapy.

Oral infections commonly originate from an odontogenic source in adults and from tonsil and lymphatic sources in children. Odontogenic infections arise from advanced dental caries or periodontal disease. Oral trauma, radiation injury, chemotherapy mucositis, salivary gland infection, lymph node abscess, and postoperative infection are potential nonodontogenic sources of infections that could potentially be life threatening. This article reviews the serious nature and potential danger that exists from oral infection and the antibiotics available to treat them are reviewed. Successful treatment requires an understanding of the microflora, the regional anatomy, the disease process, the treatment methods available, and interdisciplinary team collaboration.