Emerging Infectious Diseases Volume 18 Issue 6

2012·4.5 MB·English

by  CDC

Peer-Reviewed Journal Tracking and Analyzing Disease Trends pages 901–1040
EDITOR-IN-CHIEF
D. Peter Drotman
Managing Senior Editor EDITORIAL BOARD
Polyxeni Potter, Atlanta, Georgia, USA
Dennis Alexander, Addlestone, Surrey, UK
Associate Editors Timothy Barrett, Atlanta, Georgia, USA
Paul Arguin, Atlanta, Georgia, USA Barry J. Beaty, Ft. Collins, Colorado, USA
Charles Ben Beard, Ft. Collins, Colorado, USA Martin J. Blaser, New York, New York, USA
Ermias Belay, Atlanta, Georgia, USA Christopher Braden, Atlanta, Georgia, USA
David Bell, Atlanta, Georgia, USA Arturo Casadevall, New York, New York, USA
Sharon Bloom, Atlanta, GA, USA Kenneth C. Castro, Atlanta, Georgia, USA
Mary Brandt, Atlanta, Georgia, USA Louisa Chapman, Atlanta, Georgia, USA
Corrie Brown, Athens, Georgia, USA Thomas Cleary, Houston, Texas, USA
Charles H. Calisher, Ft. Collins, Colorado, USA Vincent Deubel, Shanghai, China
Michel Drancourt, Marseille, France Ed Eitzen, Washington, DC, USA
Paul V. Effl er, Perth, Australia Daniel Feikin, Baltimore, Maryland, USA
David Freedman, Birmingham, Alabama, USA Anthony Fiore, Atlanta, Georgia, USA
Peter Gerner-Smidt, Atlanta, Georgia, USA Kathleen Gensheimer, Cambridge, Massachusetts, USA
Stephen Hadler, Atlanta, Georgia, USA Duane J. Gubler, Singapore
Nina Marano, Atlanta, Georgia, USA Richard L. Guerrant, Charlottesville, Virginia, USA
Martin I. Meltzer, Atlanta, Georgia, USA Scott Halstead, Arlington, Virginia, USA
David Morens, Bethesda, Maryland, USA David L. Heymann, London, UK
J. Glenn Morris, Gainesville, Florida, USA Charles King, Cleveland, Ohio, USA
Patrice Nordmann, Paris, France Keith Klugman, Atlanta, Georgia, USA
Tanja Popovic, Atlanta, Georgia, USA Takeshi Kurata, Tokyo, Japan
Didier Raoult, Marseille, France S.K. Lam, Kuala Lumpur, Malaysia
Pierre Rollin, Atlanta, Georgia, USA Stuart Levy, Boston, Massachusetts, USA
Ronald M. Rosenberg, Fort Collins, Colorado, USA John S. MacKenzie, Perth, Australia
Dixie E. Snider, Atlanta, Georgia, USA Marian McDonald, Atlanta, Georgia, USA
Frank Sorvillo, Los Angeles, California, USA John E. McGowan, Jr., Atlanta, Georgia, USA
David Walker, Galveston, Texas, USA Tom Marrie, Halifax, Nova Scotia, Canada
J. Todd Weber, Atlanta, Georgia, USA Philip P. Mortimer, London, UK
Fred A. Murphy, Galveston, Texas, USA
Founding Editor
Barbara E. Murray, Houston, Texas, USA
Joseph E. McDade, Rome, Georgia, USA
P. Keith Murray, Geelong, Australia
Senior Associate Editor, Emeritus Stephen M. Ostroff, Harrisburg, Pennsylvania, USA
Brian W.J. Mahy, Bury St. Edmunds, Suffolk, UK David H. Persing, Seattle, Washington, USA
Copy Editors Claudia Chesley, Karen Foster, Thomas Gryczan, Richard Platt, Boston, Massachusetts, USA
Jean Michaels Jones, Carol Snarey, P. Lynne Stockton Gabriel Rabinovich, Buenos Aires, Argentina
Mario Raviglione, Geneva, Switzerland
Production Carrie Huntington, Ann Jordan, Shannon O’Connor,
David Relman, Palo Alto, California, USA
Reginald Tucker
Connie Schmaljohn, Frederick, Maryland, USA
Editorial Assistant Christina Dzikowski Tom Schwan, Hamilton, Montana, USA
Ira Schwartz, Valhalla, New York, USA
Social Media/Communications Sarah Logan Gregory
Tom Shinnick, Atlanta, Georgia, USA
Emerging Infectious Diseases is published monthly by the Centers for Disease Bonnie Smoak, Bethesda, Maryland, USA
Control and Prevention, 1600 Clifton Road, Mailstop D61, Atlanta, GA 30333, Rosemary Soave, New York, New York, USA
USA. Telephone [phone], fax [phone], email [email protected]. P. Frederick Sparling, Chapel Hill, North Carolina, USA
The opinions expressed by authors contributing to this journal do not neces- Robert Swanepoel, Pretoria, South Africa
sarily refl ect the opinions of the Centers for Disease Control and Prevention or Phillip Tarr, St. Louis, Missouri, USA
the institutions with which the authors are affi liated. Timothy Tucker, Cape Town, South Africa
All material published in Emerging Infectious Diseases is in the public do-
Elaine Tuomanen, Memphis, Tennessee, USA
main and may be used and reprinted without special permission; proper citation,
John Ward, Atlanta, Georgia, USA
however, is required.
Use of trade names is for identifi cation only and does not imply endorsement Mary E. Wilson, Cambridge, Massachusetts, USA
by the Public Health Service or by the U.S. Department of Health and Human
Services. ∞ Emerging Infectious Diseases is printed on acid-free paper that meets the requirements
of ANSI/NISO 239.48-1992 (Permanence of Paper)
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 6, June 2012
June 2012
On the Cover
Gerard van Kuijl,
Dutch painter active
in Rome (1604–1673) Trends in Invasive Infection
Narcissus (c. 1645) with Methicillin-Resistant
Oil on canvas
Staphylococcus aureus,
(114 cm × 143 cm)
Connecticut, 2001–2010 .....917
Collection of The John and Mable
J. L. Hadler et al.
Ringling Museum of Art, http://
www.ringling.org/ The State Art Decreases in health care–related
Museum of Florida, a division of
isolates accounted for all reductions
Florida State University
in MRSA during 2007–2010.
About the Cover p. 1034
Synopsis Molecular Epidemiology of
Geographically Dispersed
Vibrio cholerae, Kenya,
January 2009–May 2010 .....................925
A.A. Mohamed et al.
Iatrogenic Creutzfeldt-Jakob
Disease, Final Isolates represent multiple genetic lineages,
indicating multiple emergences from endemic
Assessment ........................901
reservoirs.
P. Brown et al.
Disease recognition and disinfection
practices should continue to Community Survey after Rabies
minimize new cases until a blood
Outbreaks, Flagstaff, Arizona ............932
screening test is validated. p. 935
A.M. McCollum et al.
Educational outreach should inform the public
Research about dangers of translocation of wild animals
and focus on veterinarians and physicians.
Trichomonas vaginalis
Pretransplant Fecal Carriage
Antimicrobial Drug Resistance
of Extended-Spectrum
p. 947 in 6 US Cities, 2009–2010...................939
β-Lactamase–producing
R.D. Kirkcaldy et al.
Enterobacteriaceae and
Such isolates should undergo drug susceptibility
Infection after Liver
testing periodically to detect emerging resistance.
Transplant, France ..............908
F. Bert et al.
Transplant candidates should be Virulence Potential of Fusogenic
systematically screened for carriage, Orthoreoviruses..................................944
and posttransplant infection in A.H. Wong et al.
carriers should be treated with
Virus evolution should be monitored because
carbapenems.
frequent reassortment creates the potential for
more severe infections.
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 6, June 2012
Intrafamilial Circulation of
Tropheryma whipplei, France ............949
F. Fenollar et al. June 2012
High prevalence within families might refl ect a
986 Avian Infl uenza A (H5N1) Virus
specifi c immune condition.
Antibodies in Poultry Cullers,
South Korea, 2003–2004
D. Kwon et al.
Human Gyrovirus DNA in
Human Blood, Italy .............................956
F. Maggi et al. 989 Bartonella vinsonii subsp.
arupensis in Humans,
Virus detection in blood suggests the infection
might be systemic. Thailand
Y. Bai et al.
Dispatches
992 Immunodefi ciency-associated
960 Clostridium diffi cile Infection, Vaccine-Derived Poliovirus
United States Type 3 in Infant, South Africa
J.L. Kuntz et al. p. 977 N. Gumede et al.
963 Severe Fever with 995 Rickettsia parkeri Infection
Thrombocytopenia Syndrome in Domestic Dogs, Southern
Virus, Shandong Province, Louisiana, 2011
China B.J. Grasperge et al.
L. Zhao et al.
998 Wild Boars as Hosts of
966 Macrolide-Resistant Bordetella Human-Pathogenic Anaplasma
pertussis Infection in Newborn phagocytophilum Variants
Girl, France J. Michalik et al.
S. Guillot et al.
1002 Local Transmission of Imported
969 Genome Analysis of Rift Valley p. 1005 Endemic Syphilis, Canada, 2011
Fever Virus, Mayotte S. Fanella et al.
C. Cêtre-Sossah et al.
Letters
972 Prevalence of Rift Valley Fever
among Ruminants, Mayotte 1005 Schmallenberg Virus in Calf
C. Cêtre-Sossah et al. Born at Term with Porencephaly,
Belgium
976 Louping Ill in Goats, Spain, 2011
A. Balseiro et al. 1006 Zoonotic Disease Pathogens in
Fish Used for Pedicure
979 Accuracy of ICD-10 Codes for
Surveillance of Clostridium 1008 Rickettsia conorii Indian Tick
diffi cile Infections, France Typhus Strain and R. slovaca in
G. Jones et al. Humans, Sicily
982 Molecular Epidemiology of 1010 Detection of European Strain of
Laguna Negra Virus, Mato Echinococcus multilocularis in
Grosso State, Brazil North America
E.S. Travassos da Rosa et al.
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 6, June 2012
1026 African Swine Fever Virus
Strain Georgia 2007/1 in Ticks
June 2012
1028 Triclabendazole-Resistant
1012 Recognition and Diagnosis of
Human Fasciola hepatica
Cryptococcus gattii Infections
Infection, the Netherlands
in the United States
1030 Possibility of Leishmaniasis
1015 Coccidioidal Endophthalmitis
Transmission in Jura, France
in Immunocompetent Person,
California
1030 Etymologia: Prion
1016 Human MRSA Isolates with
Novel Genetic Homolog, 1031 Hepatitis E Virus Infection in
Germany Sheltered Homeless Persons,
p. 1007
France (response)
1019 ESBL-Positive Enterobacteria
Isolates in Drinking Water Book Review
1020 Novel Chlamydiaceae Disease 1033 Mayo Clinic Infectious
in Captive Salamanders p. 1029 Diseases Board Review
1022 Novel Variant of Beilong
About the Cover
Paramyxovirus in Rats, China
1034 I rhyme / To see myself, to set
1024 Pneumococcal Serotype– the darkness echoing
specifi c Unresponsiveness in
Vaccinated Child with Cochlear
Etymologia
Implant
997 Syphilis
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 6, June 2012
Helping CDC Do More, Faster
Established by Congress as an independent, nonprofit
organization, the CDC Foundation connects the Centers for
Disease Control and Prevention (CDC) with private-sector
organizations and individuals to build public health programs
that support CDC’s work 24/7 to save lives and protect people
from health, safety and security threats.
Since 1995, the CDC Foundation has provided more than
$300 million to support CDC’s work, launched more than 500
programs around the world and built a network of individuals
and organizations committed to supporting CDC and public
health.
Each CDC Foundation program involves a talented team of
experts at CDC and at least one outside funding partner.
Sometimes, a program begins with a CDC scientist who has a
great idea and wants to collaborate with an outside partner
to make it happen. At other times, organizations in the
private sector recognize that they can better accomplish their
own public health goals by working with CDC through the
CDC Foundation.
JOIN US www.cdcfoundation.org
Photos: David Snyder / CDC Foundation
Iatrogenic Creutzfeldt-Jakob
Disease, Final Assessment
Paul Brown, Jean-Philippe Brandel, Takeshi Sato, Yosikazu Nakamura, Jan MacKenzie,
Robert G. Will, Anna Ladogana, Maurizio Pocchiari, Ellen W. Leschek, and Lawrence B. Schonberger
Medscape, LLC is pleased to provide online continuing medical education (CME) for this journal article, allowing clinicians
the opportunity to earn CME credit.
This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation
Council for Continuing Medical Education through the joint sponsorship of Medscape, LLC and Emerging Infectious Diseases.
Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians.
Medscape, LLC designates this Journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit(s)TM.
Physicians should claim only the credit commensurate with the extent of their participation in the activity.
All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME
activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 70%
minimum passing score and complete the evaluation at www.medscape.org/journal/eid; (4) view/print certificate.
Release date: May 16, 2012; Expiration date: May 16, 2013
Learning Objectives
Upon completion of this activity, participants will be able to:
• Distinguish the principal sources of iatrogenic CJD
• Identify countries with the highest rates of documented CJD
• Analyze the clinical presentation of iatrogenic CJD
• Assess new threats which might promote higher rates of CJD.
CME Editor
P. Lynne Stockton, Technical Writer/Editor, Emerging Infectious Diseases. Disclosure: P. Lynne Stockton has disclosed no
relevant financial relationships.
CME Author
Charles P. Vega, MD, Health Sciences Clinical Professor; Residency Director, Department of Family Medicine, University of
California, Irvine. Disclosure: Charles P. Vega, MD, has disclosed no relevant financial relationships.
Authors
Disclosures:Paul Brown; Jean-Philippe Brandel; Takeshi Sato, MD; Yosikazu Nakamura, MD, MPH, FFPH; Jan MacKenzie;
Anna Ladogana; Ellen W. Leschek, MD; and Lawrence B. Schonberger, MD, MPH, have disclosed no relevant financial
relationships.Robert G. Will, FRCP, has disclosed the following relevant financial relationships: served as an advisor or consultant
for LFB, Farring. Maurizio Pocchiari, MD, has disclosed the following relevant financial relationships: served as an advisor or
consultant for LFB, Farring.
The era of iatrogenic Creutzfeldt-Jakob disease (CJD) long incubation periods are still appearing. The principal
has nearly closed; only occasional cases with exceptionally sources of these outbreaks are contaminated growth
hormone (226 cases) and dura mater grafts (228 cases)
Author affi liations: Centre à l’Energie Atomique, Fontenay-aux- derived from human cadavers with undiagnosed CJD
Roses, France (P. Brown); Institut National de la Santé et de la infections; a small number of additional cases are caused
Recherche Médicale, Paris, France (J.-P. Brandel); Nanohana by neurosurgical instrument contamination, corneal grafts,
Clinic, Tokyo, Japan (T. Sato); Jichi Medical University, Yakushiji, gonadotrophic hormone, and secondary infection with
Japan (Y. Nakamura); Western General Hospital, Edinburgh, variant CJD transmitted by transfusion of blood products.
No new sources of disease have been identifi ed, and
Scotland, UK (J. MacKenzie, R.G. Will); Istituto Superiore de
current practices, which combine improved recognition of
Sanità, Rome, Italy (A. Ladogana, M. Pocchiari); National Institutes
potentially infected persons with new disinfection methods
of Health, Bethesda, Maryland, USA (E.W. Leschek); and Centers
for fragile surgical instruments and biological products,
for Disease Control and Prevention, Atlanta, Georgia, USA (L.B.
should continue to minimize the risk for iatrogenic disease
Schonberger)
until a blood screening test for the detection of preclinical
infection is validated for human use.
DOI: http://dx.doi.org/10.3201/eid1806.120116
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 6, June 2012 901
SYNOPSIS
The fi rst case of what would eventually become a in 2004, as a result of the delayed appearance of bovine
major outbreak of iatrogenic Creutzfeldt-Jakob spongiform encephalopathy in those countries.
disease (CJD) was reported in 1974; the patient had The long incubation periods—years to decades—
received a corneal transplant from an infected cadaver (1). of these low-dose infections pose a particularly diffi cult
In the years that followed, other sources of infection were problem for public health offi cials, whose recommendations
identifi ed: stereotactic electroencephalogram electrodes, may diminish the number of new cases but are impotent
neurosurgical instruments, cadaveric dura mater and when it comes to preventing cases in already-infected
pituitary glands, and, most recently, secondary variant persons in the preclinical phase of disease. It is worth
CJD (vCJD) blood products. The ensemble of iatrogenic remembering that the early recognition of iatrogenic
cases, including a bibliography of primary references, was sources of CJD was entirely because of a few remarkably
last reviewed in 2006 (2). Today, after nearly 40 years of astute neurologists, neurosurgeons, and, astonishingly, a
surveillance, the chronology and essential characteristics pediatric endocrinologist who pursued the unlikely (and
of iatrogenic CJD have been fi nalized, and the purpose unpopular) diagnosis of CJD in a growth hormone recipient
of this article is to present these data along with a few (3). It is true that some of these connections had the benefi t
brief comments about factors that determined the risk of comparatively short intervals between the infecting
for infection and how future risks might be foreseen and events and the onset of CJD. It is especially fortunate
avoided. from the standpoint of early recognition of the dura mater
By far the most common sources of iatrogenic disease association that the interval of 19 months between the
were human cadavers from which pituitary hormones operation and onset of symptoms in the fi rst case-patient
and dura mater grafts were obtained (Table 1; Figure); was among the shortest on record for this form of iatrogenic
the other major variety of environmentally acquired CJD (Table 2).
disease is vCJD. The incidence curves of human growth
hormone–associated and dura mater–associated CJD are Human Growth Hormone
almost superimposable; a broad peak occurred in the mid- The current worldwide total of growth hormone–
to-late 1990s, just ahead of the sharper peak incidence of associated cases of CJD is 226. Most cases occurred in
vCJD in the United Kingdom at the turn of the century. France (119 cases/1,880 recipients; attack rate 6.3%), the
The incidence in other countries peaked a few years later, United Kingdom (65 cases/1,800 recipients; attack rate
Table 1. Global distribution of cases of iatrogenic Creutzfeldt-Jakob disease*
Source of infection and no. cases
Surgical procedure Medical procedure
Dura mater Surgical EEG Corneal Growth Packed red
Country grafts instruments needles transplants† hormone‡ Gonadotropin blood cells§
Argentina 1
Australia 5 4
Austria 3 1
Brazil 2
Canada 4
Croatia 1
France 13 1 119
Germany 10 1
Ireland 1
Italy 9
Japan 142
Netherlands 5 2
New Zealand 2 6
South Korea 2
Qatar 1
South Africa 1
Spain 14
Switzerland 3 2
Thailand 1
United Kingdom 8 3 65 3
United States 4 1 29
Total 228 4 2 2 226 4 3
*EEG, electroencephalogram.
†Additional possible single cases after corneal transplant or keratoplasty (not included in table) in Japan, United Kingdom, and United States.
‡Human growth hormone given in Brazil and New Zealand was prepared in the United States; that given in Qatar was prepared in France. Additional
possible single cases with human growth hormone as source (not included in table) occurred in Sweden, Australia, and New Zealand.
§An additional asymptomatic but infected red-cell recipient died of an unrelated illness; another asymptomatic infected hemophilia patient who had been
exposed to potentially contaminated factor VIII also died of an unrelated illness (neither is included in the table).
902 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 6, June 2012
Iatrogenic Creutzfeldt-Jakob Disease
The methionine (M)/valine polymorphism at codon
129 of the PRNP gene has been examined in populations
with and without CJD in many countries; results have
varied (Table 3). Overall, it is clear that the M allele bestows
substantial susceptibility to the sporadic and the iatrogenic
forms of CJD; in consequence, the proportion of persons
with MM homozygous genotype is overrepresented in both
categories of disease (the sole exception occurred in UK
growth hormone recipients, which led to speculation that
a different strain of the pathogenic agent might have been
disseminated) (10). It is also clear that, as a group, persons
with heterozygous genotype had longer incubation periods
than did those with homozygous genotype, particularly in
France. Notwithstanding this statistical conclusion, it is
noteworthy that several persons with MM homozygous
genotype had incubation periods >30 years, including a
patient with recently diagnosed CJD, whose incubation
period was 42 years, the current world record for any type
of iatrogenic disease.
Incubation periods for the total case population (not just
Figure. Annual incidence of variant Creutzfeldt-Jakob disease
(vCJD) caused by ingestion of meat products contaminated with those examined for the codon 129 genotype) ranged from 5
bovine spongiform encephalopathy agent (A) and iatrogenic CJD to 42 years (mean 17 years), based on the interval between
caused by contaminated dura mater (B) and cadaveric human growth the midpoint date of what was almost always a multiyear
hormone (C), 1982–2011. White bars in panel A represent cases
period of treatment and the onset of CJD symptoms; the
from outside the United Kingdom, which were delayed in parallel with
actual date of infection is impossible to determine. Mean
the later appearance of bovine spongiform encephalopathy outside
the United Kingdom (not a second wave resulting from codon 129 incubation periods for cases in the United States and New
genotype differences). Two patients are excluded: 1 presymptomatic Zealand (patients received hormone made in the United
patient from the United States who received human growth hormone States) were 22 and 26 years; United Kingdom, 20 years;
and died of an intercurrent illness and 1 dura mater recipient from the
and France, 13 years. The shorter incubation periods in
United Kingdom with disease onset in 1978.
France could have resulted partly from the narrower limit
for the date of infection in France and are in accord with the
3.6%), and the United States (29 cases/7,700 recipients; mean incubation period of 13.5 years in the 4 gonadotropin
attack rate 0.4%). recipients from Australia, for whom there is an even more
In France, further epidemiologic observations have precise date of infection. However, a greater contribution
revealed that all 119 cases occurred within a 1,170-patient probably came from different infectious doses received by
cohort receiving treatment during a 20-month period, from patients in the different countries. Among all patients, the
December 1983 through July 1985, when there seems clinical features were distinctive in that, unlike sporadic
to have been substantial contamination resulting from CJD, signs and symptoms almost never included dementia,
sourcing and processing defi ciencies. According to these which, if it occurred at all, was typically a late component
numbers, the attack rate for the at-risk cohort in France of the clinical course.
increases to 10.2%. No new case has been identifi ed since
2008. In the United Kingdom, no cohort pattern is evident, Dura Mater
and cases continue to occur at an average rate of about 2 The worldwide tally of dura mater–associated cases is
per year (only 1 in 2011). In the United States, CJD has not 228, and new cases still continue to occur here and there,
occurred in any patient who started treatment after 1977, the most recent being individual cases in Austria, South
when a highly selective column chromatography step was Korea, and the Netherlands in 2011. If the pharmaceutical
introduced into the purifi cation protocol. Since 2003, only industry (in contrast to government-sponsored laboratories)
2 new cases have been identifi ed (1 in 2007 and 1 in 2009). comes away from the growth hormone story with an almost
An estimated ≈2,700 patients received treatment before untainted record—only 1 case has been attributed to
1977, so the attack rate in the United States for this at- industrially prepared hormone (11)—the same cannot be
risk cohort increases to 1.1% (4). The revised attack rates said about the private sector producing dura mater grafts.
therefore become 10.2% in France, 3.6% in the United The source of almost all infections was a manufacturer in
Kingdom, and 1.1% in the United States. Germany, B. Braun Melsungen AG, which has a worldwide
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 6, June 2012 903
SYNOPSIS
Table 2. Incubation periods and clinical presentations of iatrogenic Creutzfeldt-Jakob disease, according to source of infection*
Source of Infection No. cases Mean incubation period, y (range) Clinical signs†
Dura mater graft 228 12 (1.3–30) Cerebellar, visual, dementia
Neurosurgical instruments 4 1.4 (1–2.3) Visual, dementia, cerebellar
Stereotactic EEG needles 2 1.3, 1.7 Dementia, cerebellar
Corneal transplant 2 1.5, 27 Dementia, cerebellar
Growth hormone 226 17 (5–42)‡ Cerebellar
Gonadotropin 4 13.5 (12–16) Cerebellar
Packed red blood cells§ 3 6.5, 7.8, 8.3 Psychiatric, sensory, dementia, cerebellar
*EEG, electroencephalogram.
†In order of decreasing frequency.
‡Averages and ranges were 13 (5–24) y in France; 20 (7–39) y in the United Kingdom; and 22 (10–42) y in the United States.
§An additional asymptomatic but infected red-cell recipient died of an unrelated illness; another asymptomatic infected hemophilia patient who had been
exposed to potentially contaminated factor VIII also died of an unrelated illness (neither is included in the table).
distribution network, and the incidence of CJD appears to Delineation of high-risk categories initially focused
have more or less paralleled the frequency with which this on precisely those groups of persons who were exposed
source of dura mater was used. In Japan, it is estimated to the known sources of iatrogenic disease: recipients of
that as many as 20,000 patches may have been used each cadaveric dura mater grafts or pituitary-derived hormones.
year, and the 142 cases in that country constitute two thirds When vCJD started to occur, restrictions were also placed
of the global total. Nevertheless, the overall attack rate in on donor time of residence in the most heavily infected
the at-risk patient population in Japan is <0.03%. For the regions—the United Kingdom and, to a lesser extent,
entire (worldwide) group of dura mater–recipient patients, continental Europe—and embargoes were placed on the
incubation periods ranged from 1.3 to 30 years (mean 12 importation of biological products from these regions.
years), and, except in Japan, the clinical and neuropathologic These deferral and import restrictions remain in place
features were similar to those of sporadic CJD. In Japan, today and need some thoughtful reevaluation in view of
approximately one third of the cases had atypical features the near extinction of all such sources of iatrogenic CJD.
(slow progression, noncharacteristic electroencephalogram In the United States, there have been only 4 cases of dura
tracings, plaque deposition, and an atypical prion protein mater–associated disease (the most recent in 2005) and no
molecular signature on Western blots), which suggested case of growth hormone–associated CJD for anyone who
the possibility of 2 different strains of infecting agent began treatment after 1977.
(12,13). One patient had fl orid plaques and a pulvinar sign On the other hand, the possibility of iatrogenic
on magnetic resonance imaging, mimicking vCJD (5). infection resulting from transfer of tissues or fl uids from
Evaluation of the infl uence of the codon 129 genotype persons who have contracted a prion disease from animals
is complicated by the fact that the population in Japan, has not disappeared with the abating epidemics of bovine
among whom most cases occurred, has a high frequency spongiform encephalopathy and vCJD. A few persons
of the M allele (>90%), which dominated sporadic and who may be experiencing a long incubation phase of
dura mater–associated forms of CJD (Table 3) (6–9,14,15). vCJD still pose an obvious danger in the United Kingdom,
Among the cases in persons not from Japan, the distribution but an underappreciated potential danger lies in 2 other
of genotypes approximated that found among patients with animal diseases: scrapie and chronic wasting disease
sporadic CJD, and, as with growth hormone–associated (CWD). Although scrapie-infected sheep tissues have
cases, incubation periods were somewhat longer for persons been consumed for long enough (hundreds of years) to be
with heterozygous than with homozygous genotypes. considered harmless for humans, the same cannot be said
about the atypical strains of scrapie that are beginning to
Current Prevention Strategies displace the typical strains and with which we do not yet
The best way to abolish secondary iatrogenic infections have enough experience to evaluate human pathogenicity.
is, obviously, to prevent primary infections, but without Similarly, we cannot declare with certainty that CWD
a test to identify infected but asymptomatic persons, we poses no threat to humans, and CWD is continuing its
cannot entirely eliminate the risk inherent in human-to- unchecked spread across the United States and Canada with
human tissue transfer. We are therefore obliged to rely on no guarantee that it will not become globally distributed
the default strategies of 1) identifi cation and donor deferral in the years to come. One hunter has already put a group
of persons at higher than normal risk for CJD development of unwitting persons at risk for infection by donating a
and 2) inclusion of prion-reduction steps in the sterilization deer, later found to have CWD, for consumption at a rural
of penetrating instruments and the processing of therapeutic banquet in New York State (16); more such exposures are
tissues and fl uids. likely to occur as CWD continues its geographic expansion.
904 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 6, June 2012