Search

Nucleic acid testing (NAT) for hepatitis C virus (HCV) is recommended for screening of organ donors, yet not all donor infections may be detected. We describe three US clusters of HCV transmission from donors at increased risk for HCV infection. Donor's and recipients' medical records were reviewed. Newly infected recipients were interviewed. Donor-derived HCV infection was considered when infection was newly detected after transplantation in recipients of organs from increased risk donors. Stored donor sera and tissue samples were tested for HCV RNA with high-sensitivity quantitative PCR. Posttransplant and pretransplant recipient sera were tested for HCV RNA. Quasispecies analysis of hypervariable region-1 was used to establish genetic relatedness of recipient HCV variants. Each donor had evidence of injection drug use preceding death. Of 12 recipients, 8 were HCV-infected-6 were newly diagnosed posttransplant. HCV RNA was retrospectively detected in stored samples from donor immunologic tissue collected at organ procurement. Phylogenetic analysis showed two clusters of closely related HCV variants from recipients. These investigations identified the first known HCV transmissions from increased risk organ donors with negative NAT screening, indicating very recent donor infection. Recipient informed consent and posttransplant screening for blood-borne pathogens are essential when considering increased risk donors.

A liver, heart, iliac vessel and two kidneys were recovered from a 39-year-old man who died of traumatic head injury and were transplanted into five recipients. The liver recipient 18 days posttransplantation presented with headache, ataxia and fever, followed by rapid neurologic decline and death. Diagnosis of granulomatous amebic encephalitis was made on autopsy. Balamuthia mandrillaris infection was confirmed with immunohistochemical and polymerase chain reaction (PCR) assays. Donor and recipients' sera were tested for B. mandrillaris antibodies. Donor brain was negative for Balamuthia by immunohistochemistry and PCR; donor serum Balamuthia antibody titer was positive (1:64). Antibody titers in all recipients were positive (range, 1:64-1:512). Recipients received a four- to five-drug combination of miltefosine or pentamidine, azithromycin, albendazole, sulfadiazine and fluconazole. Nausea, vomiting, elevated liver transaminases and renal insufficiency were common. All other recipients survived and have remained asymptomatic 24 months posttransplant. This is the third donor-derived Balamuthia infection cluster described in solid organ transplant recipients in the United States. As Balamuthia serologic testing is only available through a national reference laboratory, it is not feasible for donor screening, but may be useful to determine exposure status in recipients and to help guide chemotherapy.

We describe four solid-organ transplant recipients with donor-derived West Nile virus (WNV) infection (encephalitis 3, asymptomatic 1) from a common donor residing in a region of increased WNV activity. All four transplant recipients had molecular evidence of WNV infection in their serum and/or cerebrospinal fluid (CSF) by reverse transcription polymerase chain reaction (RT-PCR) testing. Serum from the organ donor was positive for WNV IgM but negative for WNV RNA, whereas his lymph node and spleen tissues tested positive for WNV by RT-PCR. Combination therapy included intravenous immunoglobulin (4 cases), interferon (3 cases), fresh frozen plasma with WNV IgG (2 cases), and ribavirin (1 case). Two of the four transplant recipients survived.Review of the 20 published cases of organ-derived WNV infection found that this infection is associated with a high incidence of neuroinvasive disease (70%) and severe morbidity and mortality (30%). Median time to onset of symptomatic WNV infection was 13 days after transplantation (range 5-37 days). Initial unexplained fever unresponsive to antibiotic therapy followed by rapid onset of neurologic deficits was the most common clinical presentation. Confirmation of infection was made by testing serum and CSF for both WNV RNA by RT-PCR and WNV IgM by serological assays. Treatment usually included supportive care, reduction of immunosuppression, and frequent intravenous immunoglobulin. The often negative results for WNV by current RT-PCR and serological assays and the absence of clinical signs of acute infection in donors contribute to the sporadic occurrence of donor-derived WNV infection. Potential organ donors should be assessed for unexplained fever and neurological symptoms, particularly if they reside in areas of increased WNV activity.

Microsporidia are spore-forming, obligately intracellular organisms related to fungi. Enterocytozoon bieneusi and 3 Encephalitozoon species (Encephalitozoon cuniculi, Encephalitozoon hellem, and Encephalitozoon intestinalis) are the most common microsporidia identified as pathogens of humans (1, 2). Studies indicate that asymptomatic microsporidial disease occurs in humans, and seroprevalence data suggest that humans may be frequently exposed to these organisms (3–5). Microsporidia cause a spectrum of disease, from self-limiting diarrhea to disseminated, life-threatening infections. Microsporidiosis is recognized predominantly among HIV-infected patients but has more recently been noted in non–HIV-infected individuals as an emerging pathogen (6, 7). Several reports describe microsporidial infections involving organ transplant recipients, but to our knowledge, these infections have not been proved to be transplant-transmitted (8–11). In February 2012, the Centers for Disease Control and Prevention (CDC) was notified of a cluster of 3 transplant recipients with febrile illness onset 7 to 10 weeks after receiving organs from a common donor. Initial evaluation included serologic, molecular, and culture-based assays against a broad range of bacterial, fungal, and viral pathogens. Concomitant illnesses, such as urinary tract infection and organ rejection, were appropriately treated, yet recipients remained ill. Subsequent diagnostic evaluation of recipients suggested infections with a Brucella species that were presumed to be donor-derived. However, despite directed therapy for brucellosis and continued empirical treatment for other infectious etiologies, the patients did not improve, and assistance was requested from public health authorities in determining a common cause for the illness cluster. Kidney biopsy samples sent to CDC from 1 recipient confirmed the diagnosis as microsporidiosis with Encephalitozoon cuniculi, and a public health investigation was initiated to confirm the diagnosis in the other recipients, assess donor and recipient risk factors, and provide therapy recommendations for ill recipients.

Ehrlichiosis is a tick-borne disease that ranges in severity from asymptomatic infection to fatal sepsis. Ehrlichiosis acquired from transfusion of blood products has not been documented in the literature to date. A case of Ehrlichia ewingii infection likely transmitted by transfusion of leukoreduced platelets is described, and public health implications are discussed.

Parenteral nutrition (PN) is widely used in healthcare settings to deliver critical nutrients to patients unable to tolerate enteral feeding. The intravenous formulation is intended to provide all daily nutritional requirements, such as electrolytes, amino acids, dextrose, and lipids, and is considered to be one of the most complex pharmaceuticals to prepare because of the need for careful titration and combination of multiple components [1, 2]. Preparation under rigorous sterile conditions is especially crucial as the nutrient-rich formulation can act as favorable growth media for microorganisms [3, 4] and because the process requires the multistep transfer of several ingredients into a single container, providing opportunities for microbial contamination during the compounding process [5]. In the United States, PN can be compounded in a healthcare facility, outsourced to a compounding pharmacy, or purchased as manufactured, premixed formulations [5]. Healthcare facilities that administer PN to patients often lack the time, expertise, and technology to produce these solutions in their own facilities. As a result, the preparation of PN is frequently outsourced to compounding pharmacies specializing in these practices. In 2011, approximately 43% of 556 US hospitals with >600 beds randomly surveyed reported outsourcing their nutrition support preparations [6]. Compounding pharmacies are expected to adhere to current standards for preparation and handling of compounded sterile preparations (CSPs). One such standard is the United States Pharmacopeia's (USP) General Chapter “Pharmaceutical Compounding—Sterile Preparations,” which details conditions and practices that minimize risks of contamination of CSPs, including PN [7]. Additional standards for compounding PN solutions also exist [8, 9]. The adoption of strict standards for sterile compounding have contributed to a decline in the burden of contaminated PN preparations, and US outbreaks related to mishandling of PN during compounding are rare [2]. However, compounding CSPs, especially using nonsterile active pharmaceutical ingredients (APIs), involves challenging and complex processes, and outbreaks associated with improperly compounded preparations are being increasingly reported [10–20]. In March 2011, the Centers for Disease Control and Prevention (CDC) was notified of 5 patients with Serratia marcescens bloodstream infection (BSI) in one hospital in Alabama. Receipt of PN from a single compounding pharmacy was identified as a potential common source. The pharmacy was an independent, state-licensed compounding pharmacy in Birmingham that was registered with the Alabama State Board of Pharmacy and subject to the state laws and regulations pertaining to the compounding of parenteral therapy [21]. During the outbreak period, the pharmacy supplied PN to 6 healthcare facilities (5 acute care hospitals and 1 long-term acute care hospital), all located within Alabama. Prescriptions for PN were received daily by the pharmacy, and compounded PN preparations were delivered to hospitals each night. On 15 March 2011, after being notified of these S. marcescens BSIs, the pharmacy voluntarily ceased all compounding activities and subsequently recalled all CSPs as a precautionary measure. An investigation was conducted by the Alabama Department of Public Health and CDC to determine the extent of the outbreak, identify risk factors for infection among PN recipients, and review PN compounding practices to identify potential sources of contamination.

We identified West Nile virus (WNV) RNA in skin, fat, muscle, tendon, and bone marrow from a deceased donor associated with WNV transmission through solid organ transplantation. WNV could not be cultured from the RNA-positive tissues. Further studies are needed to determine if WNV can be transmitted from postmortem tissues.