Transplantation-Transmitted Tuberculosis—Oklahoma and Texas, 2007 FREE

MMWR. 2008;57:333-336

Approximately 28,000 organ transplants were performed in the United States in 2007.¹ When infections are transmitted from donors, the implications can be serious for multiple recipients.^2- 4 Tuberculosis (TB), a known infectious disease complication associated with organ transplantation, occurs in an estimated 0.35%-6.5% of organ recipients in the United States and Europe posttransplantation.² In 2007, the Oklahoma State Department of Health identified Mycobacterium tuberculosis in an organ donor 3 weeks after the donor's death. This report summarizes results of the subsequent investigation, which determined that disseminated TB occurred in two of three transplant recipients from this donor, and one recipient died. Genotypes of the donor and recipient TB isolates were identical, consistent with transmission of TB by organ transplantation. To reduce the risk for TB transmission associated with organ transplantation, organ recovery personnel should consider risk factors for TB when assessing all potential donors. In addition, clinicians should recognize that transplant recipients with TB might have unusual signs or symptoms. When transmission is suspected, investigation of potential donor-transmitted TB requires rapid communication among physicians, transplant centers, organ procurement organizations (OPOs), and public health authorities.

In April 2007, a U.S.-born man aged 46 years with a history of seizure disorder, alcoholism, homelessness, and incarceration was admitted to an Oklahoma hospital for presumed alcohol withdrawal seizures and aspiration pneumonitis. He had a prolonged hospitalization characterized by altered mental status, fever, persistent pneumonia, hydrocephalus, multifocal cerebral infarction, and progressive neurologic disability attributed to cerebral vasculitis. The patient continued to decline neurologically and met clinical criteria for brain death in early June 2007. Organs were recovered for transplantation, and the liver and kidneys were transplanted into three recipients, all Texas residents, at facilities in Oklahoma and Texas. Three weeks after the organ donor's death, a culture from cerebrospinal fluid obtained as part of his clinical evaluation for fever and altered mental status grew M. tuberculosis. Subsequently, M. tuberculosis also was cultured from stored donor spleen tissue.

The donor had been treated for presumed aspiration pneumonia with left lower lobe infiltrate and pleural effusion in December 2006, 6 months before his death. In March 2007, 1 month before his final hospitalization, the donor was again hospitalized for community-acquired pneumonia, shown on chest radiograph as involving the left upper and left lower lobe. He had no recognized history of TB or foreign travel and had not been identified as a contact of any person with TB. Two tuberculin skin tests (TSTs) performed during the 6 months before his death (one required by a homeless shelter, the other performed by the jail) were negative. No specimen was obtained for acid-fast bacilli (AFB) examination or mycobacterial culture.

Recipient A. A woman aged 50 years received one of the donor's kidneys. In late July 2007, 6 weeks after the kidney transplant, she developed fever, followed by pancytopenia and a sepsis-like syndrome. At notification in late July the donor's positive culture for M. tuberculosis, a bone marrow aspirate was smear positive for AFB. Despite subsequent treatment with anti-TB therapy, the recipient died 9 weeks posttransplantation. The primary causes of death listed after autopsy were disseminated TB, leukopenia, and end-stage renal disease. M. tuberculosis was cultured from the deceased recipient's blood, liver, spleen, and lungs. The polymerase chain reaction (PCR)-based genotype and restriction fragment length polymorphism (RFLP) pattern of the recipient's M. tuberculosis isolate matched those of the donor.

Recipient B. A woman aged 23 years received the donor's other kidney, and had fever and severe headache in late July, 7 weeks after transplantation and concurrent with notification of the donor's positive M. tuberculosis culture. She was started on anti-TB medications. Her cerebrospinal fluid was negative on AFB smear and culture. Pancytopenia developed; although the patient's bone marrow aspirate revealed granulomas, the smear was negative for AFB. M. tuberculosis subsequently grew from the recipient's blood and urine specimens; these isolates had a PCR-based genotype and RFLP pattern matching that of the donor. The recipient experienced renal allograft dysfunction in August 2007, approximately 10 weeks after transplantation. Biopsy of the allograft revealed interstitial nephritis with negative AFB smear and culture; anti-TB medications were adjusted, and a course of low-dose steroids was added. As of this report, the patient was doing well, had stable renal allograft function, and was tolerating anti-TB medications.

Recipient C. The liver recipient, a man aged 59 years, was started on anti-TB treatment 2 months posttransplantation and had no symptoms of TB. Granulomas suggestive of mycobacterial infection were detected from a routine posttransplantation liver biopsy in January 2008, 7 months posttransplantation, while the recipient continued anti-TB treatment. AFB smear was negative, and culture identified Mycobacterium avium complex, a nontuberculous species of mycobacteria. No M. tuberculosis was cultured.

Contact investigations were conducted to evaluate at-risk hospital workers, close personal contacts, and family members related to the donor and recipients. No transmission of TB infection has been documented through contact investigation.

V Kohli, MD, Integris Baptist Medical Center, Oklahoma City; L Smithee, MS, Oklahoma State Dept of Health. K Ishihara, MD, Univ of Texas Medical Branch at Galveston; L Ostrosky-Zeichner, MD, C Van Buren, MD, J Lappin, MD, Univ of Texas Health Science Center at Houston. T Harrington, MD, Div of Tuberculosis Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention; M Kuehnert, MD, Div of Healthcare Quality Promotion, National Center for Preparedness, Detection, and Control of Infectious Diseases; E Piercefield, MD, DVM, EIS Officer, CDC.

The majority of TB cases among organ transplant recipients are caused by activation of latent tuberculosis infection (LTBI) in the recipient once immunosuppressive medications are started to prevent organ rejection; a minority are attributed to donor transmission. In one international study, 4% of TB infections in recipients were considered donor derived.² In this case report, genotyping supported the conclusion that transmission of TB occurred by organ transplantation to two recipients from a common donor. Although organ procurement protocols were followed, pretransplantation screening did not identify TB in the donor.

In the United States, all potential organ donors are screened to prevent transmission of infectious diseases, including TB, by organ transplantation. Minimum standards for donor eligibility are defined by United Network for Organ Sharing (UNOS), a nonprofit, private organization under government contract with the Health Resources and Services Administration to coordinate U.S. transplant activities.⁵ To evaluate eligibility, (1) the donor's medical record is reviewed for specific conditions (such as known active TB), (2) a medical and social history is conducted with next of kin (or other suitable person familiar with the donor), and (3) selected laboratory testing (such as testing for human immunodeficiency virus, hepatitis, and good organ function) and a chest radiograph are performed. No standard assessment is conducted to determine specifically whether the potential donor is at risk for having previously undiagnosed TB or LTBI. Although the screening process might uncover symptoms or risk factors for TB or LTBI, no further investigation or diagnostic testing is required. For all patients who are eligible by UNOS definitions, each OPO devises its own process for donor acceptance. The donor's medical and social history obtained by the OPO is made available for review by transplant center clinicians to independently assess risk for transmission of infection before accepting the organs for transplantation. The completeness and accuracy of this background information is variable, however, because often such information is obtained secondhand by interview of persons familiar with the donor.

Early recognition of posttransplantation TB in the recipient is critical for successful treatment. The incidence of TB among organ recipients is as much as 74 times that of the general population.² In addition, 49% of U.S. transplant recipients with TB have disseminated disease, and 38% die.² Extrapulmonary and disseminated diseases are common, leading to atypical signs that might not be easily recognized as TB if unsuspected by the clinician. In transplant patients, TB should be considered in the differential diagnosis of persistent fever, pneumonia, meningitis, septic arthritis, pyelonephritis, septicemia, graft rejection, or bone marrow suppression. Clinicians should recognize that the presence of an unusual constellation of symptoms, particularly during the first few weeks after transplantation, raises the possibility of donor-transmitted infection or activation of LTBI. Even with a high index of suspicion, TB in an organ recipient can be challenging to diagnose: 75%-80% of organ recipients who developed TB had a false-negative pretransplantation TST,⁶ and in this immunosuppressed population, symptoms of TB might be attributed to other potential complications, including organ rejection or other infectious diseases.

Diagnosis of TB in an organ recipient, in the absence of clear risk factors or other evidence from pretransplantation screening, should prompt investigation of possible transmission from the donor. Other recipients from a common donor might be at risk and should be evaluated for TB. When transplantation-transmitted TB is suspected, health-care providers should alert the associated OPO, tissue bank, and public health authorities.

To prevent TB transmission by transplantation, specific policies can be established to improve recognition of disease in donors. In 2004, the American Society of Transplantation developed guidelines to assist in pretransplantation screening of potential organ donors and recipients.^6- 7 These recommendations are not mandatory standards and, therefore, are not necessarily incorporated into OPO standard operating procedures. OPOs can enhance their pretransplantation screening protocols by incorporating these guidelines to identify risk factors for unrecognized TB in the donor. If risk factors are found, further mycobacterial testing and radiologic assessment is warranted. For risk factor assessment, OPOs should obtain donor history of symptoms consistent with active TB, past diagnosis of TB infection (active or latent), homelessness, excess alcohol or injection-drug use, incarceration, recent exposure to persons with active TB, or travel to areas where TB is endemic. Complete donor medical and social histories should be provided to transplant centers.

Regardless of risk factor assessment, testing for M. tuberculosis (e.g., AFB smear or mycobacterial culture) whenever clinical specimens for routine bacterial testing are obtained from donors can help ensure detection of unrecognized TB. In addition, routine retention of samples of donor tissues and serum from organ procurement (or from autopsy) that are suitable for laboratory evaluation can aid subsequent transmission investigations. Genotyping and other relatedness testing of isolates can help establish or rule out transmission links between donor and recipients, as demonstrated in this report. OPOs also should follow up on results of all tests pending at the time of organ donation and notify transplant centers immediately of any results that might have implications for recipients. Because not all disease transmission through transplantation can be prevented, rapid recognition is critical to facilitate appropriate treatment, minimize complications, enhance patient safety, and improve public health.

This report is based, in part, by contributions by B Baker, MPH, S Pennington, Oklahoma City, P Lindsey, MD, C Harvey, DO, Oklahoma State Dept of Health Tuberculosis Div, S Mallonee, MPH, Oklahoma State Dept of Health, M Spinner, P Eddington, Oklahoma City County Tuberculosis Control Center; M Lambert, Cleveland County Health Dept; C Wallace, PhD, P Cruise, Texas Dept of State Health Svcs, K Finkel, MD, A Wanger, PhD, Univ of Texas Medical School at Houston, M Abramsky, MD, Houston Dept of Health and Human Svcs, S Haidry, MD, Galveston County Health District, B Seaworth, MD, Heartland National Tuberculosis Center, San Antonio; E Desmond, PhD, California Dept of Health Svcs; J Hager, MPH, United Network for Organ Sharing, Richmond, Virginia; D Seem, MPH, Div of Healthcare Quality Promotion, National Center of Preparedness, Detection, and Control of Infectious Diseases, V Tomlinson, MPA, P Moonan, DrPH, Div of Tuberculosis Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC.