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APR 0 8 2008


Morbidity and Mortality Weekly Report GOVERNMENT PUBLICATIONS DEPT.

Transplantation-Transmitted Tuberculosis

Approximately 28,000 organ transplants were performed
n the United States in 2007 (1). When infections are trans-
nitted from donors, the implications can be serious for
multiple recipients (2-4). Tuberculosis (TB), a known
nfectious disease complication associated with organ trans-
plantation, occurs in an estimated 0.35%-6.5% of organ
ecipients in the United States and Europe posttrans-
plantation (2). In 2007, the Oklahoma State Department
of Health identified Mycobacterium tuberculosis in an organ
Honor 3 weeks after the donor's death. This report summa-
izes results of the subsequent investigation, which deter-
nined that disseminated TB occurred in two of three
ransplant recipients from this donor, and one recipient
died. Genotypes of the donor and recipient TB isolates were
dentical, consistent with transmission of TB by organ trans-
olantation. To reduce the risk for TB transmission associ-
ited with organ transplantation, organ recovery personnel
hould consider risk factors for TB when assessing all
potential donors. In addition, clinicians should recognize
hat transplant recipients with TB might have unusual signs
or symptoms. When transmission is suspected, investigation
of potential donor-transmitted TB requires rapid communi-
ation among physicians, transplant centers, organ procure-
nent organizations (OPOs), and public health authorities.

Case Report

Organ Donor. In April 2007, a U.S.-born man aged 46
ears with a history of seizure disorder, alcoholism,
omelessness, and incarceration was admitted to an Okla-
oma hospital for presumed alcohol withdrawal seizures
nd aspiration pneumonitis. He had a prolonged hospital-
ation characterized by altered mental status, fever, persis-
ent pneumonia, hydrocephalus, multifocal cerebral
farction, and progressive neurologic disability attributed

April 4, 2008 / Vol. 57 / No. 13
Oklahoma and Texas, 2007

to cerebral vasculitis. The patient continued to decline neu-
rologically 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 recipi-
ents, 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 evalua-
tion 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 effu-
sion 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 pneu-
monia, 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 con-
tact 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.


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The MMWR series of publications is published by the Coordinating Center for Health Information and Service, Centers for Disease Control and Prevention (CDC), U.S. Department of Health and Human Services, Atlanta, GA 30333.

Suggested Citation: Centers for Disease Control and Prevention. [Article title]. MMWR 2008;57: [inclusive page numbers].

Centers for Disease Control and Prevention
Julie L. Gerberding, MD, MPH


Tanja Popovic, MD, PhD Chief Science Officer

James W. Stephens, PhD

Associate Director for Science

Steven L. Solomon, MD

Director, Coordinating Center for Health Information and Service Jay M. Bernhardt, PhD, MPH

Director, National Center for Health Marketing

Katherine L. Daniel, PhD

Deputy Director, National Center for Health Marketing

Editorial and Production Staff

Frederic E. Shaw, MD, JD
Editor, MMWR Series
Teresa F. Rutledge

(Acting) Managing Editor, MMWR Series
Douglas W. Weatherwax
Lead Technical Writer-Editor
Donald G. Meadows, MA
Jude C. Rutledge
Peter M. Jenkins

(Acting) Lead Visual Information Specialist
Lynda G. Cupell

Malbea A. LaPete

Visual Information Specialists Quang M. Doan, MBA

Erica R. Shaver

Information Technology Specialists

Editorial Board

William L. Roper, MD, MPH, Chapel Hill, NC, Chairman
Virginia A. Caine, MD, Indianapolis, IN
David W. Fleming, MD, Seattle, WA
William E. Halperin, MD, DrPH, MPH, Newark, NJ
Margaret A. Hamburg, MD, Washington, DC
King K. Holmes, MD, PhD, Seattle, WA
Deborah Holtzman, PhD, Atlanta, GA
John K. Iglehart, Bethesda, MD
Dennis G. Maki, MD, Madison, WI
Sue Mallonee, MPH, Oklahoma City, OK
Stanley A. Plotkin, MD, Doylestown, PA
Patricia Quinlisk, MD, MPH, Des Moines, IA
Patrick L. Remington, MD, MPH, Madison, WI
Barbara K. Rimer, DrPH, Chapel Hill, NC
John V. Rullan, MD, MPH, San Juan, PR
Anne Schuchat, MD, Atlanta, GA
Dixie E. Snider, MD, MPH, Atlanta, GA
John W. Ward, MD, Atlanta, GA

Recipient A. A woman aged 50 years received one of the donor's kidneys. In late July 2007, 6 weeks after the kid ney transplant, she developed fever, followed by pancytop nia and a sepsis-like syndrome. At notification in late Ju the donor's positive culture for M. tuberculosis, a bone ma row aspirate was smear positive for AFB. Despite subs quent treatment with anti-TB therapy, the recipient di 9 weeks posttransplantation. The primary causes of deat 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. Th polymerase chain reaction (PCR)-based genotype and restriction fragment length polymorphism (RFLP) patter of the recipient's M. tuberculosis isolate matched those o the donor.

Recipient B. A woman aged 23 years received the donors 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 cerebrospi nal fluid was negative on AFB smear and culture. Pancy topenia developed; although the patient's bone marrow aspirate revealed granulomas, the smear was negative for AFB. M. tuberculosis subsequently grew from the recipients blood and urine specimens; these isolates had a PCR-based genotype and RFLP pattern matching that of the dono 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 posttransplan tation and had no symptoms of TB. Granulomas sugges tive 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 mem bers related to the donor and recipients. No transmission of TB infection has been documented through contact investigation.

Reported by: V Kohli, MD, Integris Baptist Medical Center, Oklahoma City; L Smithee, MS, Oklahoma State Dept of Health. KIshihara, MD Univ of Texas Medical Branch at Galveston; L Ostrosky-Zeichner, MD

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 or Preparedness, Detection, and Control of Infectious Diseases; E Piercefield, MD, DVM, EIS Officer, CDC.

Editorial Note: The majority of TB cases among organ ransplant recipients are caused by activation of latent uberculosis infection (LTBI) in the recipient once immunosuppressive medications are started to prevent organ ejection; a minority are attributed to donor transmission. -n one international study, 4% of TB infections in recipients were considered donor derived (2). In this case report, zenotyping supported the conclusion that transmission of TB occurred by organ transplantation to two recipients from I common donor. Although organ procurement protocols vere followed, pretransplantation screening did not identify [B in the donor.

In the United States, all potential organ donors are creened to prevent transmission of infectious diseases, ncluding TB, by organ transplantation. Minimum stanlards for donor eligibility are defined by United Network or Organ Sharing (UNOS), a nonprofit, private organizaion under government contract with the Health Resources nd Services Administration to coordinate U.S. transplant activities (5). To evaluate eligibility, 1) the donor's medical ecord is reviewed for specific conditions (such as known ictive 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 ll patients who are eligible by UNOS definitions, each OPO devises its own process for donor acceptance. The onor'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. efore accepting the organs for transplantation. The comleteness and accuracy of this background information is ariable, however, because often such information is btained secondhand by interview of persons familiar with me donor.

Early recognition of posttransplantation TB in the ecipient is critical for successful treatment. The incidence f 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, healthcare 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.


1. Organ Procurement and Transplantation Network. Transplant data [Database]. Richmond, VA: Organ Procurement and Transplantation Network; 2008. Available at

2. Singh N, Paterson DL. Mycobacterium tuberculosis infection in solidorgan transplant recipients: impact and implications for management. Clin Infect Dis 1998;27:1266-77.

3. Delmonico F. Cadaver donor screening for infectious agents in solid organ transplantation. Clin Infec Dis 2000;31:781-6.

4. Wilck M, Fishman J. The challenges of infection in transplantation: donor-derived infections. Curr Opin Organ Transplant 2005;10:301–6. 5. United Network for Organ Sharing. Minimum procurement standards for an organ procurement organization (OPO). Richmond, VA: United Network for Organ Sharing; 2001. Available at policiesandbylaws/policies.asp.

6. American Society of Transplantation. Mycobacterium tuberculosis. Am J Transplant 2004;4(Suppl 10):S37-41. Available at

7. American Society of Transplantation. Screening of donor and recipient prior to solid organ transplantation. Am J Transplant 2004;4 (Suppl 10):S10-20. Available at ajt/4/s10.

Nonfatal Maltreatment

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of Infants United States, October 2005-September 2006 During October 2005-September 2006 (federal fisc year 2006), approximately 905,000 U.S. children were vi tims of maltreatment that was substantiated by state and local child protective services (CPS) agencies (1).* Approx mately 19% of child maltreatment fatalities occurred amor infants (i.e., persons aged <1 year) (1), and homicide sta tistics suggest that fatality risk might be greatest in the first week of life (2). However, the risk for nonfatal matreatment among infants has not been examined previous at the national level. To determine the extent of nonfata infant maltreatment in the United States, CDC and the federal Administration for Children and Families (ACF analyzed data collected in fiscal year 2006 (the most recent data available) from the National Child Abuse and Neglect Data System (NCANDS). This report summarize the results of that analysis, which indicated that, in fisca year 2006, a total of 91,278 infants aged <1 year (rate 23.2 per 1,000 population) experienced nonfatal maltreatment, including 29,881 (32.7%) who were aged ≤1 week Neglect was the maltreatment category cited for 68.5% 0: infants aged ≤1 week, but NCANDS data did not permit further characterization of the nature of this neglect. Developing effective measures to prevent maltreatment o infants aged <1 week will require more detailed characterization of neglect in this age group.

NCANDS is a national data collection and analysis system created in response to the federal Child Abuse Prevention and Treatment Act. Data have been collected annually from states and reported since 1993. States submit caselevel data as child-specific records for each report of alleged child maltreatment for which a completed investigation of assessment by a CPS agency has been made during the reporting period. Individual CPS agencies are responsible for determining the type of maltreatment and outcome of the maltreatment investigation based on state and federa laws. However, no standardized definitions of maltreatment are used consistently by all states; therefore, each state maps its own classification of maltreatment onto NCANDS

*Substantiated maltreatment is defined as maltreatment by a parent or other caregiver deemed to have occurred after thorough investigation by a qualified stati member from a CPS agency with jurisdiction over the geographic area in which the maltreatment took place. Additional information is available at http:

* Public Law 93-247 as amended. Additional information is available at http:/

definitions before sending the final data file to NCANDS. Once a state submits its data to NCANDS, a technical alidation review is conducted by a staff supervised by the ACF Children's Bureau to assess the internal consistency of he data and to identify probable causes for missing data. States are requested to make corrections as needed.

In fiscal year 2006, 49 states, the District of Columbia, and Puerto Rico provided case-level data to NCANDS. For his report, data from five states (Alaska, Maryland, North Dakota, Pennsylvania, and Vermont) were not available for analysis. Only data regarding victims with a CPS agency disposition of substantiated maltreatment issued during iscal year 2006 were analyzed. Among the approximately 3.6 million children aged <18 years who were subjects of naltreatment investigations in fiscal year 2006, maltreatnent was substantiated by CPS agencies in approximately 905,000 (25.1%) children. Substantiated maltreatment data were analyzed for victims aged <1 year by the age of he infant victim at the time of first report, sex, race/ ethnicity, type of maltreatment, and source of the report. A total of 91,278 unique victims of substantiated malreatment were identified in CPS agency dispositions in iscal year 2006 among infants aged <1 year, an annual rate of 23.2 per 1,000 population. A total of 47,117 51.6%) victims were male. By race/ethnicity, 39,768 43.6%) infant victims were white; 23,008 (25.2%) were black or African American; 17,582 (19.3%) were Hispanic; 1,141 (1.3%) were American Indian or Alaska Native; and 583 (0.6%) were Asian. Multiple race/ethnicity was identified for 2,874 (3.1%) of the infant victims, and 6,322 (6.9%) were of unknown race/ethnicity.

Among the 91,278 infant victims of substantiated maltreatment, 35,455 (38.8%) were aged <1 month (Figure 1). Of these, 29,881 (84.3%) were aged <1 week (Figure 2). Among maltreated infants aged <1 week, 20,472 (68.5%) were categorized as victims of neglect (including deprivation of necessities or medical neglect), and 3,957 (13.2%) as victims of physical abuse (Table).

Categories of maltreatment in NCANDS are as follows: physical abuse, neglect or deprivation of necessities, medical neglect, sexual abuse, psychological or emotional maltreatment, other, and unknown. For this report, neglect or deprivation of necessities and medical neglect were combined into one category; other and unknown maltreatments also were combined into one category. Examples of neglect under the NCANDS categories include educational neglect, abandonment, fetal alcohol syndrome, and congenital drug exposure or addiction. Since 2003, NCANDS has used a method for compiling racial/ethnic data based on the 1997 revised Office of Management and Budget standards for race and ethnicity, which include the following racial categories: white, black or African American, Asian, American Indian or Alaska Native, and Native Hawaiian or Other Pacific Islander. In NCANDS, persons categorized as Hispanic or Latino are not categorized by race.

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