Clinical Infectious Diseases
1 December 2014
Volume 59
Number 11
The title Clinical Infectious Diseases is a registered trademark of the IDSA
i News
iii In the Literature
ARTICLES AND COMMENTARIES
1511 Clinical and Laboratory Findings of the First Imported Case of Middle
East Respiratory Syndrome Coronavirus to the United States
On the cover: Miracle of Hope, 2010, acrylic on
canvas, by David Putnam (American, born 1958).
Stanford University Positive Care Clinic, Atherton,
CA. Reproduced with permission of the artist.
Antiretroviral treatment in the last decade of
the 20th century marked the turning of the tide in
the battle against AIDS. Inspired by the patients
and staff of the Positive Care Clinic in Atherton,
California, the artist David Putnam created a
triptych to be displayed in the clinic, illustrating the
new hope for those affected by HIV. The panel on
the left, the centerpiece of the original triptych,
depicts the protease inhibitors (blue dots) pitted
against the HIV with its protease enzyme complex
(in black). In the right panel, the bright yellow
background expresses the triumph of therapy as
the virus is diminished and hope shines through, or
as Mr. Putnam described, “The good guys began
winning.”
(Mary & Michael Grizzard, Cover Art Editors)
Minal Kapoor, Kimberly Pringle, Alan Kumar, Stephanie Dearth, Lixia Liu, Judith Lovchik, Omar Perez,
Pam Pontones, Shawn Richards, Jaime Yeadon-Fagbohun, Lucy Breakwell, Nora Chea, Nicole J. Cohen,
Eileen Schneider, Dean Erdman, Lia Haynes, Mark Pallansch, Ying Tao, Suxiang Tong, Susan Gerber,
David Swerdlow, and Daniel R. Feikin
The ﬁrst US case of Middle East respiratory syndrome coronavirus was conﬁrmed in May 2014 in
a 65-year-old physician who worked in Saudi Arabia and presented to an Indiana hospital on illness
day 11. He had bilateral pneumonia and recovered fully.
1519 Impact of Inﬂuenza B Lineage-Level Mismatch Between Trivalent
Seasonal Inﬂuenza Vaccines and Circulating Viruses, 1999–2012
Terho Heikkinen, Niina Ikonen, and Thedi Ziegler
Throughout 12 recent seasonal inﬂuenza outbreaks in Finland, inﬂuenza B viruses representing the
other genetic lineage than the one included in the vaccine accounted for 42% of all inﬂuenza B
infections and 11% of all inﬂuenza infections in the population.
1525 Editorial Commentary: Changing Epidemiology of Inﬂuenza B Virus
W. Paul Glezen
1527 Insufﬁcient Fluconazole Exposure in Pediatric Cancer Patients and the
Need for Therapeutic Drug Monitoring in Critically Ill Children
Kim C. M. van der Elst, Marieke Pereboom, Edwin R. van den Heuvel, Jos G. W. Kosterink,
Elisabeth H. Schölvinck, and Jan-Willem C. Alffenaar
The ﬂuconazole serum concentration is signiﬁcantly lower in pediatric cancer patients and the
ﬂuconazole concentration negatively correlates with the time to culture conversion. Therapeutic drug
monitoring of ﬂuconazole is potentially a valuable tool to detect underexposure in critically ill children.
1534 Editorial Commentary: Fluconazole Therapeutic Drug Monitoring in
Children With Cancer: Not Today
Michael Cohen-Wolkowiez and Daniel K. Benjamin Jr
1537 Preformed Frequencies of Cytomegalovirus (CMV)–Speciﬁc Memory T
and B Cells Identify Protected CMV-Sensitized Individuals Among
Seronegative Kidney Transplant Recipients
Marc Lúcia, Elena Crespo, Edoardo Melilli, Josep M. Cruzado, Sergi Luque, Inés Llaudó, Jordi Niubó,
Joan Torras, Núria Fernandez, Josep M. Grinyó, and Oriol Bestard
Monitoring preformed cytomegalovirus (CMV)–speciﬁc T- and B-cell memory immune responses,
using novel functional immune assays, may allow accurate characterization of antiviral immune
sensitization in kidney transplant recipients, regardless of CMV-speciﬁc serological proﬁle, illustrating
the risk for posttransplant CMV infection.
1546 An Outbreak of Respiratory Tularemia Caused by
Diverse Clones of Francisella tularensis
Anders Johansson, Adrian Lärkeryd, Micael Widerström, Sara Mörtberg,
Kerstin Myrtännäs, Caroline Öhrman, Dawn Birdsell, Paul Keim,
David M. Wagner, Mats Forsman, and Pär Larsson
Whole-genome sequences of Francisella tularensis isolated from 10
patients involved in a respiratory tularemia outbreak were compared with
110 global archived isolates. Surprisingly, outbreak and archived isolates
were often extremely similar despite sometimes great separation in time
and/or space.
1554 Association Between Recent Use of Proton Pump
Inhibitors and Nontyphoid Salmonellosis: A
Nested Case-Control Study
Hau-Hsin Wu, Yung-Tai Chen, Chia-Jen Shih, Yi-Tzu Lee, Shu-Chen Kuo,
and Te-Li Chen
The association between oral proton pump inhibitors and nontyphoid
salmonellosis continues to be debated. In the current study we found a
signiﬁcant temporal association with or without matching for
independent predisposing factors.
1559 Signiﬁcant Clinical Impact of a Rapid Molecular
Diagnostic Test (Genotype MTBDRplus Assay) to
Detect Multidrug-Resistant Tuberculosis
Maia Kipiani, Veriko Mirtskhulava, Nestani Tukvadze, Matthew Magee,
Henry M. Blumberg, and Russell R. Kempker
Implementation of a rapid molecular diagnostic for the detection of
multidrug-resistant tuberculosis (MDR-TB) led to decreased times to
initiation of second-line drug treatment, culture conversion, and
decreased the length of time MDR-TB patients were hospitalized on
drug-susceptible TB wards.
1567 Both Lewis and Secretor Status Mediate
Susceptibility to Rotavirus Infections in a
Rotavirus Genotype–Dependent Manner
Johan Nordgren, Sumit Sharma, Filemon Bucardo, Waqas Nasir,
Gökçe Günaydın, Djeneba Ouermi, Leon W. Nitiema, Sylvia Becker-Dreps,
Jacques Simpore, Lennart Hammarström, Göran Larson, and
Lennart Svensson
We describe host genetic factors determining susceptibility to
rotavirus infection and report that Lewis-negative and secretor-negative
children are resistant to P[8] rotavirus strains, but not to P[6] rotavirus
strains, providing a plausible explanation to reduced vaccine efﬁcacy in
some populations.
1574 Uniform Research Case Deﬁnition Criteria
Differentiate Tuberculous and Bacterial
Meningitis in Children
Regan S. Solomons, Marie Wessels, Douwe H. Visser, Peter R. Donald,
Ben J. Marais, Johan F. Schoeman, and Anne M. van Furth
A uniform tuberculous meningitis (TBM) research case deﬁnition was
developed to address low numbers of culture-conﬁrmed cases. The
performance of the case deﬁnition was evaluated in culture-conﬁrmed
TBM and bacterial meningitis. “Probable TBM” criteria accurately
differentiated TBM from bacterial meningitis.
1579 Simeprevir (TMC435) With Pegylated Interferon/
Ribavirin in Patients Coinfected With HCV
Genotype 1 and HIV-1: A Phase 3 Study
Douglas Dieterich, Jürgen Kurt Rockstroh, Chloe Orkin, Félix Gutiérrez,
Marina B. Klein, Jacques Reynes, Umesh Shukla, Alan Jenkins,
Oliver Lenz, Sivi Ouwerkerk-Mahadevan, Monika Peeters,
Guy De La Rosa, Lotke Tambuyzer, and Wolfgang Jessner
Simeprevir 150mg with peginterferon/ribavirin (24 or 48 weeks)
resulted in high sustained virologic response rates at 12 weeks in
patients with hepatitis C virus (HCV) genotype-1/HIV-1 coinfection,
irrespective of prior HCV or HIV treatment, METAVIR score or HCV
genotype/subtype.
BRIEF REPORT
1588 Treating Progressive Multifocal
Leukoencephalopathy With Interleukin 7 and
Vaccination With JC Virus Capsid Protein VP1
Mireia Sospedra, Sven Schippling, Sara Yousef, Ilijas Jelcic,
Silvia Boﬁll-Mas, Raquel Planas, Jan-Patrick Stellmann, Viktoria Demina,
Paola Cinque, Robert Garcea, Therese Croughs, Rosina Girones, and
Roland Martin
VIEWPOINTS
1593 Infectious Diseases Subspecialty: Declining
Demand Challenges and Opportunities
Pranatharthi Chandrasekar, Daniel Havlichek, and Leonard B. Johnson
A signiﬁcant decline in the number of applicants for infectious
diseases fellowship positions has been noted in recent years. Most
reduction is seen among international medical graduates. Reasons for
the decline are speculated upon and possible solutions are offered.
INVITED ARTICLE
1599 FOOD SAFETY
Seroincidence of Human Infections With
Nontyphoid Salmonella Compared With Data
From Public Health Surveillance and Food
Animals in 13 European Countries
Kåre Mølbak, Jacob Simonsen, Charlotte S. Jørgensen,
Karen A. Krogfelt, Gerhard Falkenhorst, Steen Ethelberg,
Johanna Takkinen, and Hanne-Dorthe Emborg
Antibody measurements were applied to estimate the rate of
Salmonella infections in humans. Data obtained from 13 European
countries correlated with the Salmonella prevalence in food animals
and estimates of travel-associated Salmonella infections but not
with the reported national incidence.
HIV/AIDS
1607 The Effect of Therapeutic Lumbar Punctures on
Acute Mortality From Cryptococcal Meningitis
Melissa A. Rolfes, Kathy Huppler Hullsiek, Joshua Rhein,
Henry W. Nabeta, Kabanda Taseera, Charlotte Schutz, Abdu Musubire,
Radha Rajasingham, Darlisha A. Williams, Friedrich Thienemann,
Conrad Muzoora, Graeme Meintjes, David B. Meya, and
David R. Boulware
Intracranial pressure management with repeat lumbar puncture (LP)
was investigated in patients with cryptococcal meningitis in sub-Saharan
Africa. Conducting at least 1 additional LP soon after cryptococcal
diagnosis was related to decreased risk of acute mortality regardless of
initial pressure.
1615 Editorial Commentary: An Expanded Role for
Therapeutic Lumbar Punctures in Newly
Diagnosed AIDS-Associated Cryptococcal
Meningitis?
1638 Neutrophil-Associated Central Nervous System
Inﬂammation in Tuberculous Meningitis Immune
Reconstitution Inﬂammatory Syndrome
Suzaan Marais, Katalin A. Wilkinson, Maia Lesosky, Anna K. Coussens,
Armin Deffur, Dominique J. Pepper, Charlotte Schutz, Zahiera Ismail,
Graeme Meintjes, and Robert J. Wilkinson
Tuberculous meningitis immune reconstitution inﬂammatory syndrome
(TBM-IRIS) is characterized by severe, compartmentalized cerebral
inﬂammation, involving mediators of innate and adaptive immune
responses. A high baseline cerebrospinal ﬂuid bacillary load predisposes
to recurrent inﬂammation during antiretroviral therapy, manifesting as
TBM-IRIS.
CORRESPONDENCE
1648 Clostridium difﬁcile Infection and Candida
Colonization of the Gut: Is There a Correlation?
Giammarco Raponi, Valeria Visconti, Grazia Brunetti, and
Maria Cristina Ghezzi
Peter G. Pappas
1618 Hepatitis B Virus Sub-genotype A1 Infection Is
Characterized by High Replication Levels and
Rapid Emergence of Drug Resistance in
HIV-Positive Adults Receiving First-line
Antiretroviral Therapy in Malawi
Samir Aoudjane, Mas Chaponda, Antonio Adrián González del Castillo,
Jemma O’Connor, Marc Noguera, Apostolos Beloukas, Mark Hopkins,
Saye Khoo, Joep J. van Oosterhout, and Anna Maria Geretti
HBV sub-genotype A1 has a severe virologic expression among
HIV-positive Malawians, contrasting with the mild outcomes observed
elsewhere. By deep sequencing, HBV drug-resistance was universal in
viremic patients receiving lamivudine/stavudine/nevirapine, with faster
emergence than previously estimated by Sanger sequencing.
1627 A Prospective Cohort Study of Neurocognitive
Function in Aviremic HIV-Infected Patients
Treated With 1 or 3 Antiretrovirals
Ignacio Pérez-Valero, Alicia González-Baeza, Miriam Estébanez,
Susana Monge, María L. Montes-Ramírez, Carmen Bayón,
Federico Pulido, José I. Bernardino, Francisco X. Zamora,
Juan J. González-García, María Lagarde, Asunción Hernando,
Francisco Arnalich, and José R. Arribas
A prospective study showed no relevance of the number of
antiretrovirals used to preserve neurocognitive function in aviremic
human immunodeﬁciency virus (HIV)–positive patients, with important
implications concerning HIV-associated neurocognitive disorders and the
use of nucleoside-sparing regimens.
1635 Editorial Commentary: Protease Inhibitor
Monotherapy: Safe for the CNS in Durably
Suppressed Patients?
Scott L. Letendre
1649 Defective Antigen Tubes Generate False-Positive
QuantiFERON Tuberculosis Test Results
Marc Roger Couturier, Robbie Myatt, Don Dorn, David T. Yang, and
Nancy Pitstick
1650 Mortality in Patients With AIDS-Related
Cytomegalovirus Retinitis in Myanmar
NiNi Tun, Frank M. Smithuis, Nikolas London, W. Lawrence Drew, and
David Heiden
1651 Added Value of the emm-Cluster Typing System
to Analyze Group A Streptococcus Epidemiology
in High-Income Settings
Stanford T. Shulman, Robert R. Tanz, James B. Dale, Andrew C. Steer,
and Pierre R. Smeesters
1652 Diagnosis of Central Nervous System Mycoses in
Solid Organ Transplant Recipients
Spinello Antinori, Laura Milazzo, and Mario Corbellino
1653 Reply to Antinori et al
Alissa J. Wright and Jay A. Fishman
1654 Oral Rehydration Therapy in Cholera
Munsey Stephen Wheby
1655 A Case of Cerebrospinal Fluid Viral Escape on a
Dual Antiretroviral Regimen: Worth the Risk?
Davide Mangioni, Antonio Muscatello, Francesca Sabbatini,
Alessandro Soria, Marianna Rossi, Luca Bisi, Nicola Squillace,
Carlo De Grandi, Andrea Gori, and Alessandra Bandera
ELECTRONIC ARTICLE
e158 Intracellular Bacteria in the Pathogenesis of
Escherichia coli Urinary Tract Infection in
Children
Luciana Robino, Paola Scavone, Lucia Araujo, Gabriela Algorta,
Pablo Zunino, María Catalina Pírez, and Rafael Vignoli
Intracellular bacteria or intracellular bacterial communities (IB/IBCs)
were associated with recurrent Escherichia coli urinary tract infection
(UTI) in children without urinary tract abnormalities. Bacterial virulence
proﬁles reﬂected a wide diversity of uropathogenic E. coli. IB/IBCs could
explain a high proportion of children with recurrent UTI.
The electronic article listed above is freely available in this issue
of Clinical Infectious Diseases online (http://cid.oxfordjournals.org/
content/current ).