Download sulted in statistically significantly more toxicity than did fluconazole

sulted in statistically significantly more
toxicity than did fluconazole in the study.
Thus, we conclude that the potential benefit of posaconazole as prophylaxis for this
group of patients is not without some additional risk.
Acknowledgments
Financial support. Astellas Pharma, Enzon,
Nektar Therapeutics, Merck, Pfizer, and ScheringPlough (T.F.P.).
Potential conflicts of interest. T.J.W. has Cooperative Research & Development Agreements
with Vicuron (subsequently acquired by Pfizer)
and Fujisawa (Astellas). T.F.P. has been a consultant for Merck, Pfizer, Schering-Plough, Basilea,
Nektar Therapeutics, and Stiefel Laboratories and
has been on the speakers’ bureau for Merck, Pfizer,
and Schering-Plough.
Thomas F. Patterson1 and Thomas J. Walsh2
1
University of Texas Health Science Center at San
Antonio, San Antonio; and 2National Cancer
Institute, Bethesda, Maryland
References
1. Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guidelines
of the Infectious Diseases Society of America.
Clin Infect Dis 2008; 46:327–60.
2. Cornely OA, Maertens J, Winston DJ, et al.
Posaconazole vs. fluconazole or itraconazole
prophylaxis in patients with neutropenia. N
Engl J Med 2007; 356:348–59.
3. Ullmann AJ, Lipton JH, Vesole DH, et al. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med
2007; 356:335–47.
4. Bow EJ. Long-term antifungal prophylaxis in
high-risk hematopoietic stem cell transplant recipients. Med Mycol 2005; 43(Suppl 1):
S277–87.
5. Bow EJ, Laverdiere M, Lussier N, Rotstein C,
Cheang MS, Ioannou S. Antifungal prophylaxis
for severely neutropenic chemotherapy recipients: a meta analysis of randomized-controlled
clinical trials. Cancer 2002; 94:3230–46.
6. Falagas ME, Vardakas KZ. Liposomal amphotericin B as antifungal prophylaxis in bone marrow transplant patients. Am J Hematol 2006;
81:299–300.
7. Glasmacher A, Prentice AG. Evidence-based review of antifungal prophylaxis in neutropenic
patients with haematological malignancies. J
Antimicrob Chemother 2005; 56(Suppl 1):
i23–32.
8. Vardakas KZ, Michalopoulos A, Falagas ME.
Fluconazole versus itraconazole for antifungal
prophylaxis in neutropenic patients with haematological malignancies: a meta-analysis of
randomised-controlled trials. Br J Haematol
2005; 131:22–8.
9. Karthaus M. Treatment of aspergillosis. Clin
Infect Dis 2008; 47:427 (in this issue).
Reprints or correspondence: Dr. Thomas F. Patterson, University of Texas Health Science Center at San Antonio, Dept.
of Medicine/Infectious Diseases, 7703 Floyd Curl Dr., MSC
7881, San Antonio, TX 78229-3900 ([email protected]).
Clinical Infectious Diseases 2008; 47:427–8
2008 by the Infectious Diseases Society of America. All
rights reserved. 1058-4838/2008/4703-0021$15.00
DOI: 10.1086/589924
Presence of the A226V
Mutation in Autochthonous
and Imported Italian
Chikungunya Virus Strains
To the Editor—Recently, Stan Deresinski [1] discussed the role of the A226V
mutation in the increased fitness of chikungunya infection in the vector Aedes albopictus, which, in turn, may expand the
potential for chikungunya virus to diffuse
to the Americas and Europe as a result of
the widespread distribution of this vector
[2–5].
The recent outbreak in central Italy
drew attention to the question of why no
other outbreaks had occurred earlier in
other regions of Italy or Europe. Recently,
Rezza et al. [6] and Charrel et al. [7] listed
as major outbreak determinants the concentration of competent vectors at the
time of arrival of the index case and the
temporal overlapping of arthropod activity (i.e., seasonal synchronicity).
Because the strains that were isolated
during the Italian outbreak displayed the
A226V mutation, we analyzed the presence of the E1 molecular signatures associated with the Indian Ocean outbreak
of chikungunya infection in viral isolates
from the 2007 local outbreak and from
cases previously imported to Italy. Five
isolates from imported cases, 3 of which
occurred in individuals returning from
Mauritius in 2006 (strains ITA2_BMI_06,
ITA1_TAM_06, and ITA3_CGO_06, obtained during the period February–April
2006) and 2 of which occurred in individuals returning from India in 2006 and
2007 (strains ITA4_MRA_06, obtained in
September 2006, and strain ITA5_
JEM_07, obtained in July 2007), and 2
428 • CID 2008:47 (1 August) • CORRESPONDENCE
isolates from autochthonous cases that occurred during the 2007 Italian outbreak
(strains ITA7_BIO_07 and ITA8_VEN_07,
obtained in September 2007) were included in the sequence analysis, together
with an isolate obtained from a mosquito
during the Italian outbreak (available from
GenBank).
All 7 isolates from humans and the isolate from the mosquito carried the Indian
Ocean outbreak signature mutations
M269V and D284E. The A226V mutation
was present in each of the isolates imported from Mauritius, in the isolates obtained from the autochthonous cases from
the Italian outbreak, in the isolates obtained from the mosquito, and in the isolate imported from India in 2007, but it
was absent from the isolate obtained in
the case imported from India in 2006.
Our findings indicate that, during 2006
and 2007, multiple strains were imported
to Italy from the Indian Ocean region.
Both the imported and autochthonous
strains isolated in Italy displayed the
M269V and D284E mutations. A226V was
present in all imported and autochthonous strains, with the exception of the isolate imported from India in 2006. This is
in agreement with published data [8] and
with available GenBank sequence data, indicating that the virus strains circulating
in India in 2006 lacked this mutation. On
the contrary, according to GenBank sequence data, it appears that this mutation
is absent from the most recent isolates obtained in Singapore but is present in each
of the isolates obtained during the 2007
outbreak in India (table 1).
These data support the view that the E1
sequence of strains from India changed
over time, acquiring the mutation associated with enhanced fitness in A. albopictus after 2006. Fixation of A226V may
be a common evolution pathway in explosive outbreaks. Of note, the outbreak
in Singapore, where the virus displayed the
wild-type amino acid at position 226, was
rapidly controlled. Additional studies are
needed to appreciate the significance of
Table 1. Molecular signatures of the Indian Ocean subgroup in the E1 sequence of 7 chikungunya
virus isolates.
Chikingunya virus strain
(GenBank accession number)
a
S27 (AF 369024)
LR2006_OPY1 (DQ443544)
b
ITA1_TAM_E1 (EU188924)
ITA2_BMI_06b (EU190879)
ITA3_CGO_06b (EU190881)
IND-06-AP3 (EF027134)
MIV-69 (EU350535)
b
ITA4_MRA_06 (EU190884)
E1 mutations
Time of
isolation
Provenance
A226V
M269V
D284E
1953
2006
Tanzania
Réunion
No
Yes
No
Yes
No
Yes
February 2006
Mauritius
Yes
Yes
Yes
March 2006
April 2006
2006
Mauritius
Mauritius
India
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
Yes
2007
India
Yes
Yes
Yes
September 2006
India
No
Yes
Yes
ITA5_JEM_0 (EU272130)
b
ITA7_BIO_07 (EU272132)
ITA8_VEN_07b (EU272133)
ITA07-RA1 (EU244823)
July 2007
September 2007
India
Italy
Yes
Yes
Yes
Yes
Yes
Yes
September 2007
September 2007
Italy
c
Italy (A. albopictus)
Yes
Yes
Yes
Yes
Yes
Yes
SG EHIss622 (EU441883)
2008
Singapore
No
Yes
Yes
b
NOTE. Data are shown for 3 chikungunya virus isolates deriving from patients returning to Italy from Mauritius, 2
deriving from patients returning from India, and 2 deriving from patients involved in the 2007 Italian outbreak. The S27
prototype strain, strains from Réunion, the Indian subcontinent, and Singapore, and an isolate obtained from a mosquito
during the Italian outbreak (which had an E1 sequence that was available in GenBank) are included for comparison.
a
Prototype strain.
Strains from Italian cases, either imported or autochthonous, analyzed at the National Institute for Infectious Diseases in Rome, Italy.
c
Strain from an isolate obtained during the Italian outbreak from Aedes albopictus (Bonilauri P., personal communication); the sequence was available in GenBank.
b
this mutation for the interaction of the
virus with the vector and with humans, as
well as to predict the evolution of outbreaks both at the site of origin and in
those countries, such as Italy, to which the
virus can be imported.
Acknowledgments
We thank Carla Nisii for critically reading the
manuscript of this article.
Potential conflicts of interest. All authors: no
conflicts.
Financial support. Italian Ministry of Health,
fondi Ricerca Corrente, and Piano di Sostegno
Diagnostico Assistenziale ed Epidemiologico alle
Emergenze Biologiche sul Territorio Italiano.
Licia Bordi,1 Fabrizio Carletti,1
Concetta Castilletti,1 Roberta Chiappini,1
Vittorio Sambri,3 Francesca Cavrini,3
Giuseppe Ippolito,2 Antonino Di Caro,1 and
Maria R. Capobianchi1
1
Laboratory of Virology and 2Department of
Epidemiology, National Institute for Infectious
Diseases “L. Spallanzani”, Rome, and 3Laboratory
of Microbiology, Alma Mater Studiorum, Bologna
University, Bologna, Italy
References
1. Deresinski S. In the literature: how did chikungunya get that way? Clin Infect Dis 2008;
46:V–VI.
2. Vazeille M, Moutailler S, Coudrier D, et al. Two
chikungunya isolates from the outbreak of La
Reunion (Indian Ocean) exhibit different patterns of infection in the mosquito, Aedes albopictus. PLoS ONE 2007; 2:1–9.
3. Tsetsarkin KA, Vanlandingham DL, McGee CE,
Higgs S. A single mutation in chikungunya virus affects vector specificity and epidemic potential. PLoS Pathog 2007; 3:1895–906.
4. Charrel RN, de Lamballerie X, Raoult D. Chikungunya outbreaks—the globalization of vector-borne diseases. N Engl J Med 2007; 356:
769–71.
5. Knudsen AB, Romi R, Majori G. Occurence
and spread in Italy of Aedes albopictus, with
implications for its introduction into other
parts of Europe. J Am Mosq Control Assoc
1996; 12:177–83.
6. Rezza G, Nicoletti L, Angelini R, et al. Infection
with chikungunya virus in Italy: an outbreak
in a temperate region. Lancet 2007; 370:1840–6.
7. Charrel R, de Lamballerie X. Chikungunya in
north-eastern Italy: a consequence of seasonal
synchronicity. Euro Surveill 2008; 13:8003.
8. Arankalle VA, Shrivastava S, Cherian S, et al.
Genetic divergence of chikungunya viruses in
India (1963–2006) with special reference to the
2005–2006 explosive epidemic. J Gen Virol
2007; 88:1967–76.
Reprints or correspondence: Dr. Maria Rosaria Capobianchi,
Laboratory of Virology, Padiglione Baglivi, National Institute
for Infectious Diseases, INMI “L. Spallanzani”, Via Portuense
292, 00149 Rome, Italy ([email protected]).
Clinical Infectious Diseases 2008; 47:428–9
2008 by the Infectious Diseases Society of America. All
rights reserved. 1058-4838/2008/4703-0022$15.00
DOI: 10.1086/589925
Novel Risk Factors for
Clostridium difficile–
Associated Disease in a
Setting of Endemicity?
To the Editor—In a retrospective cohort
study involving 382 hospital admissions of
patients with Clostridium difficile–associated disease (CDAD) and 35,704 hospital
admissions of patients without CDAD,
Dubberke et al. [1] identified several risk
factors for the development of CDAD in
a setting of endemicity. Novel risk factors
included previous use of intravenous vancomycin and “CDAD pressure” (defined
CORRESPONDENCE • CID 2008:47 (1 August) • 429