To the Editor:

An unenveloped single-stranded DNA virus, TT virus (TTV), was initially identified as a transfusion-transmissible agent reported to be associated with non-A-G hepatitis by Nishizawa et al.1 At present, transfusion of blood and blood products is supposed to be a major route of TTV transmission.1,2 

In the recent report, Okamoto et al3 developed the TTV detection polymerase chain reaction (PCR) system by exchanging the primers from RD037,038,051,052 to NG059,061,063, and showed that 12% of healthy blood donors were positive for TTV in Japan. Whereas several investigators2 have used their own original primers sets located in a more homogeneous region of the TTV sequence, many investigators4,5 have used Okamoto et al’s primers in their study concerned with TTV.

More recently, Takahashi et al6 reported a newly developed PCR diagnostic system that is 10 to 100 times more sensitive than Okamoto et al’s method and detected TTV DNA in 92 (92%) of 100 individuals who visited their hospital for health screening. We used this method and measured TTV DNA in various samples as indicated in Table 1. Paired samples (upper half of Table 1) were obtained from mothers admitted to our hospital for delivery of infants this year. Serum samples of infants or children (bottom half of Table 1) were obtained from individuals during outpatient visits for minor transient diseases or health checks this year. Informed consent was obtained from all of the individuals.

Table 1.

Prevalence of TTV-DNA in Serum, Amniotic Fluid, and Milk

Samples (age) n Positive for TTV-DNA (%)
Mother’s serum* 48  43 (89.6)  
Amniotic fluid* 48  0 (0) 
Mother’s milk* 48  27 (56.3)  
Serum in umbilical cord* 48  0 (0)  
Newborn’s serum (2-3 d)* 48  0 (0)  
Infant serum (<1 yr)  6 6 (100)  
Infant serum (1 yr)  8  7 (87.5) 
Preschooler serum (2-6 yrs)  20  19 (95)  
School-ager serum (7-12 yrs)  20  18 (90) 
Samples (age) n Positive for TTV-DNA (%)
Mother’s serum* 48  43 (89.6)  
Amniotic fluid* 48  0 (0) 
Mother’s milk* 48  27 (56.3)  
Serum in umbilical cord* 48  0 (0)  
Newborn’s serum (2-3 d)* 48  0 (0)  
Infant serum (<1 yr)  6 6 (100)  
Infant serum (1 yr)  8  7 (87.5) 
Preschooler serum (2-6 yrs)  20  19 (95)  
School-ager serum (7-12 yrs)  20  18 (90) 
*

Paired samples between mothers and their children.

Positive samples are all from mothers who are positive for TTV in sera.

Two-, 4-, 6-, 9-, 10-, and 11-month-old individuals.

By using this efficient detection system,6 we obtained a surprising result that was hardly consistent with a previous report by Yamada-Osaki et al.4 According to this previous study that used Okamoto et al’s primers, the incidence of TTV infection was fairly low in infants and increased gradually in the preschool group. In contrast, our study showed that, whereas newborns are completely negative, most infants are already positive for TTV DNA even within 1 year after birth. This result apparently indicates that mother-to-child TTV infection occurs just around the baby’s birth in most cases. Our possible explanation for this is that a transmission manor may be vertical at delivery. Another possibility is that transmission occurs via mother’s milk, in which TTV DNA was fairly prevalent, as shown in Table 1.

The clinical importance of TTV has been controversial ever since its discovery. Although association of TTV with posttransfusion hepatitis,1 some groups of chronic hepatitis,3and fluminant hepatitis3 has been reported, the prevalence of TTV infection in the general population is too high to explain its specific pathogenicity. Takahashi et al6 could not detect different liver function test values between TTV-positive and -negative individuals and concluded that asymptomatic carriers of TTV are very common in the general population in Japan. Our observation of the extremely high transmission incidence at birth may explain the development of chronic TTV infection without any clinical symptoms, because infantile infection sometimes enables viruses to escape from the immune system, as evidenced in hepatitis B virus asymptomatic carriers.

REFERENCES

REFERENCES
1
Nishizawa
T
Okamoto
H
Konishi
K
Yoshizawa
H
Miyakawa
Y
Mayumi
M
A novel DNA virus (TTV) associated with elevated transaminase levels in posttransfusion hepatitis of unknown etiology.
Biochem Biophys Res Commun
241
1997
92
2
Simmonds
P
Davidson
F
Lycett
C
Prescott
LE
MacDonald
DM
Ellender
J
Yap
PL
Ludlam
CA
Haydon
GH
Gillon
J
Jarvis
LM
Detection of a novel DNA virus (TT virus) in blood donors and blood products.
Lancet
352
1998
191
3
Okamoto
H
Nishizawa
T
Kato
N
Ukita
M
Ikeda
H
Iizuka
H
Miyakawa
Y
Mayumi
M
Molecular cloning and characterization of a new DNA virus (TTV) associated with posttransfusion hepatitis of unknown etiology.
Hepatol Res
10
1998
1
4
Yamada-Osaki
M
Sumazaki
R
Noguchi
E
Shibasaki
M
Matsui
A
Transfusion transmitted virus.
Lancet
352
1998
1310
5
Schroter
M
Feucht
HH
Schafer
P
Zollner
B
Laufs
R
Fischer
L
Knodler
B
TT virus viremia and liver transplantation: No significant increase of the prevalence.
Blood
92
1998
4877
6
Takahashi
K
Hoshino
H
Ohta
Y
Yoshida
N
Mishiro
S
Very high prevalence of TT virus (TTV) infection in general population of Japan revealed by a new set of PCR primers.
Hepatol Res
12
1998
225