open reading frame) in addition to the usual IS1016-bexA deletion ...

Figure 1. A, Alignment of IS1016-V5 elements. B, Alignment of “inner” IS1016-V2 elements 

representative also of those at the 3 ′ end, identical in sequence. Strain code numbers are indicated 

on the right. Underline, start codons; double underline, stop codons; arrows, the 19-nucleotide 

inverted repeats; gray areas, deletions. 

open reading frame) in addition to the 

usual IS1016-bexA deletion, together with 

several point mutations (figure 1A). Sequencing 

of the IS1016-V2 PCR products 

(EMBL accession numbers AM268187– 

AM268189) indicated that (1) in each isolate, 

the inner IS1016 elements were identical 

in sequence to the one at the 3 ′ end 

of the cap; and (2) the nucleotide sequences 

from the 3 isolates were identical 

to each other and different from the reference 

sequence. Actually, our IS1016-V2 

sequences showed the presence of an 11bp 

gap and numerous point mutations, 

indicating that these isolates displayed 

polymorphism in all IS1016 elements (figure 

1B). Strains carrying the IS1016 variant 

sequences appeared to be closely related 

by PFGE (data not shown) and 

genetically distinct from the major Hib 

clone circulating in Italy [6]. 

Whether the variant IS1016 sequences 

described herein may influence the modulation 

of the cap b copy number requires 

further investigation. Although the inci- 

1226 • CID 2006:43 (1 November) • CORRESPONDENCE 

dence of invasive Hib disease decreased 

dramatically following introduction of 

conjugate Hib vaccines, and considering 

that the amplified state of the cap b locus 

may contribute to vaccine failure [8], concern 

about the presence of strains possessing 

an amplified cap b locus has been 

raised. To conclude, we would like to emphasize 

the importance of further molecular 

investigations of the H. influenzae cap 

genes. 

Acknowledgments 

We are very grateful to Tonino Sofia for editorial 

assistance. 

Potential conflicts of interest. All authors: no 

conflicts. 

Maria Giufrè, Rita Cardines, 

Paola Mastrantonio, and Marina Cerquetti 

Department of Infectious, Parasitic, 

and Immune-Mediated Diseases, 

Istituto Superiore di Sanità, Rome, Italy 

References 

1. Kapogiannis BG, Satola S, Keyserling HL, Farley 

MM. Invasive infections with Haemophilus 

influenzae serotype a containing an IS1016bexA 

partial deletion: possible association with 

virulence. Clin Infect Dis 2005; 41:e97–103. 

2. Kroll JS, Loynds BM, Moxon ER. The Haemophilus 

influenzae capsulation gene cluster: a 

compound transposon. Mol Microbiol 1991;5: 

1549–60. 

3. Kroll JS, Moxon ER. Capsulation and gene copy 

number at the cap locus of Haemophilus influenzae 

type b. J Bacteriol 1988; 170:859–64. 

4. Kroll JS, Moxon ER, Loynds BM. An ancestral 

mutation enhancing the fitness and increasing 

the virulence of Haemophilus influenzae type b. 

J Infect Dis 1993; 168:172–6. 

5. Corn PG, Anders J, Takala AK, Kayhty H, Hoiseth 

SK. Genes involved in Haemophilus influenzae 

type b capsule expression are frequently amplified. 

J Infect Dis 1993; 167:356–64. 

6. Cerquetti M, Cardines R, Giufrè M, et al. Genetic 

diversity of invasive strains of Haemophilus 

influenzae type b before and after introduction 

of the conjugate vaccine in Italy. Clin 

Infect Dis 2006; 43:317–9. 

7. Satola SW, Schirmer PL, Farley MM. Complete 

sequence of the cap locus of Haemophilus influenzae 

serotype b and nonencapsulated b capsule-negative 

variants. Infect Immun 2003; 71: 

3639–44. 

8. Cerquetti M, Cardines R, Ciofi degli Atti ML, 

et al. Presence of multiple copies of the capsulation 

b locus in invasive Haemophilus influenzae 

type b (Hib) strains isolated from children 

with Hib conjugate vaccine failure. J Infect 

Dis 2005; 192:819–23. 

Reprints or correspondence: Dr. Marina Cerquetti, Dept. of 

Infectious, Parasitic, and Immune-Mediated Diseases, Istituto 

Superiore di Sanità, Viale Regina Elena, 299, 00161 Roma, 

Italy (mcerquet@iss.it). 

Clinical Infectious Diseases 2006; 43:1225–6 

2006 by the Infectious Diseases Society of America. All 

rights reserved. 1058-4838/2006/4309-0024$15.00 

Prevalence of Influenza B 

during the 2004–2005 

Season in Japan 

To the Editor—We appreciate Dr. 

Baum’s comments [1] regarding our study 

[2] comparing the effectiveness of oseltamivir 

for the treatment of influenza A 

and influenza B. Baum mentions that “the 

first [factor]—unexplained—is the relatively 

high incidence of influenza B. It is 

not clear whether many more influenza A 

cases were in fact identified but not studied, 

or whether almost one-half of the 

cases of influenza identified were indeed 

influenza B. The latter would be very unusual” 

[1, p. 446]. We would like to comment 

about this. Via the internet, we collect 

almost all cases that are diagnosed 

Downloaded from 

http://cid.oxfordjournals.org/ by guest on March 21, 2013

Figure 1. The number of patients in each season surveyed by the date of onset of influenza A 

or influenza B. Percentages are the percentage of all seasonal cases of influenza attributable to 

influenza B. Median, median date of epidemic, expressed as month/day. 

with use of the commercial rapid detection 

kits in the participating clinics throughout 

Japan between 10 November and 31 May 

every year. Figure 1 shows the date of onset 

and the number of cases of influenza A 

or influenza B that were diagnosed with 

the use of rapid detection kits during the 

past 5 influenza seasons. The total number 

of influenza A or influenza B cases, the 

percentage of cases that are attributable to 

influenza B, and the median date of the 

epidemic in each season are also shown. 

The prevalence of influenza A was consistent 

in almost every year. However, the 

prevalence of influenza B was variable season 

by season. The percentage of influenza 

cases attributable to influenza B was very 

small in the 2003–2004 and 2005–2006 

seasons (2.5% and 2.1%, respectively). 

However, in the 2004–2005 season, the 

number of influenza B cases was more 

than twice the number of influenza A 

cases; the percentage of influenza cases attributable 

to influenza B was 67.8%. The 

high incidence of influenza B during the 

2004–2005 season in Japan (also available 

on the Web site of the Infectious Disease 

Surveillance Center of Japan [3]) seemed 

to be unusual, as mentioned by Baum [1]. 

We would also like to emphasize that 

all patients from whom we obtained the 

date and time of the onset of fever, the 

administration of oseltamivir, and the resolution 

of fever were included in the study, 

and no patients with influenza A or influenza 

B from whom we obtained these data 

were excluded [2]. 

In the 2004–2005 season, influenza A 

and influenza B were almost simultaneously 

prevalent (the median dates of the 

epidemics were 27 February for influenza 

A and 21 February for influenza B). It 

seems to be important to differentiate patients 

with influenza A from patients with 

influenza B by use of commercial antigen 

detection kits, particularly during seasons 

in which both types of influenza virus are 

simultaneously prevalent (such as the 

2004–2005 season), because oseltamivir is 

less effective for the treatment of influenza 

B virus, as reported elsewhere [2, 4]. 


Potential conflicts of interest. All authors: no 

conflicts. 

Naoki Kawai, 1 Hideyuki Ikematsu, 1,2 

Norio Iwaki, 1 Nobuo Hirotsu, 1 and 

Seizaburo Kashiwagi3 1Japan Physicians Association, Tokyo, and 

2 

Department of Clinical research, Hara-doi Hospital, 

and 3 Fukuoka Red Cross Blood Center, 

Fukuoka, Japan 

References 

1. Baum SG. Oseltamivir and the influenza alphabet. 

Clin Infect Dis 2006; 43:445–6. 

2. Kawai N, Ikematsu H, Iwaki N, et al. A comparison 

of the effectiveness of oseltamivir for 

the treatment of influenza A and influenza B: 

a Japanese multicenter study of the 2003–2004 

and 2004–2005 influenza seasons. Clin Infect 

Dis 2006; 43:439–44. 

3. Infectious Disease Surveillance Center of Japan. 

Weekly reports of virus isolation/detection 

2002/03–2006/07. Available at: https://hassei 

doko.mhlw.go.jp/Byogentai/Pdf/data2e.pdf. 

Accessed 20 September 2006. 

4. Kawai N, Ikematsu H, Iwaki N, et al. Factors 

influencing the effectiveness of oseltamivir and 

amantadine for the treatment of influenza: a 

CORRESPONDENCE • CID 2006:43 (1 November) • 1227 



multicenter study from Japan of the 2002–2003 

influenza season. Clin Infect Dis 2005; 40: 

1309–16. 

Reprints or correspondence: Dr. Naoki Kawai, 4-9 Tonomachi, 

Gifu City, 500-8116, Japan (nkawai@city.gifu.med.or.jp). 

Clinical Infectious Diseases 2006; 43:1226–8 



In Support of Dr. Thomas 

Butler 

To the Editor—We would like to thank 

Greenough [1] for his update on Dr. 

Thomas Butler. It is important that young 

physicians remain aware of the pitfalls that 

exist within the field of infectious diseases 

and within the academic environment. We 

are sure that all of us will now pause for 

a moment before we transport microbiologic 

agents, sign a contract with an academic 

institution, or report a missing 

specimen. To not pause would be foolish; 

the personal risks are too great. However, 

as each of you realize, it will take far more 

than a moment’s pause to assure adherence 

to new standards, and as Relman et 

al. [2] state, the losers will be life sciences 

research and the biodefense effort. 

One would hope that Tom’s horrendous 

experience will help others to avoid 

the “woods” that incarcerated him and 

robbed him of his precious medical license 

and career. We hope that some person who 

reads about his plight will find a niche that 

will provide emotional and financial relief 

to this dedicated scientist. 

We met Tom in Vietnam in 1974 while 

he was conducting research on plague and 

diarrheal diseases. We knew him to be an 

enthusiastic and diligent researcher. We 

were particularly encouraged to read 

Tom’s words and to see that he has been 

able to find employment. We are sure that 

his reunion with family and friends will 

go a long way in helping him to heal. 

Although Tom and family have led a frugal 

existence, they continue to have tremendous 

debts and to face the challenges 

of day-to-day life. 

We in the Infectious Diseases Society of 

America should reach out to Tom and his 

family with generous support, to help him 

1228 • CID 2006:43 (1 November) • CORRESPONDENCE 

overcome some of his legal debts. We 

would encourage all who can afford a donation 

to send it directly to Tom: 

Thomas Butler, M.D. 

4611 10th St. 

Lubbock, TX 79416 


Potential conflicts of interest. K.G and J.D.B: 

no conflicts. 

Kenneth Gould1,a and Joel D. Brown 2 

1Southern California Kaiser Permanente Medical 

Group, California; and 2 Department of Internal 

Medicine, University of Hawaii John A. Burns 

School of Medicine, Honolulu 

References 

1. Greenough WB. Update on Dr. Thomas Butler. 

Clin Infect Dis 2006; 43:259–60. 

2. Rellman DA, Choffines E, Lemon SM. In search 

of biosecurity. Science 2006; 311:1835. 

a Retired. 

Reprints or correspondence: Dr. Kenneth Gould (kennethgould 

@comcast.net). 

Clinical Infectious Diseases 2006; 43:1228

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