To the Editor:
Transfusion-transmitted virus (TTV), a recently identified single-stranded DNA virus, has been shown to be associated with hepatitis of unknown origin. 1,2 Although transmission has been reported to be mainly parenteral, sexual transmission has been hypothesized. 3,4 Nonetheless, according to recent studies, the low prevalence of TTV among individuals at risk for sexually or parenterally transmitted infections, such as men who have sex with men (MSM) and intravenous drug users (IDU), suggests a low efficiency of sexual behavior and practices related to intravenous drug use in the transmission of TTV. 5–6 However, these studies did not investigate the association between specific risk behaviors and TTV in these population groups.
To better understand the modalities of transmission, in June 1999 we began a serologic study to determine the prevalence and correlates of TTV viremia among persons presumably at high risk for parenterally and sexually transmitted infections (i.e., MSM and IDUs). To ensure comparability, participants were recruited in the same area; MSM were recruited from a sexually transmitted disease (STD) clinic in Rome, and IDUs were recruited from an infectious-disease reference center in Pistoia (both cities located in central Italy). Clinical and behavioral data were collected using a standard questionnaire administered by a trained interviewer. Persons with a documented history of an STD were defined as those previously treated for any STD in the center of recruitment. None of the study participants reported a history of blood transfusion.
The TTV DNA was detected in stored sera by seminested polymerase chain reaction using primers from N22 regions. 7 Sera were screened for HIV-1 antibodies using a commercial enzyme-linked immunosorbent assay (Genelavia Mix, Pasteur, France); reactive sera are confirmed with Western blot analysis (Western Blot, NevLav Blot I, Sanofi-Pasteur, France).
As of December 31, 1999, our study has recruited 185 nondrug-using MSM and 179 IDUs. Of the 179 IDUs, 26 (14.5%) were TTV-DNA positive and 18 (10.1%) were HIV-1-positive. Of the 185 MSM, 8 (4.3%) were TTV-DNA positive and 51 (27.6%) were HIV-1 positive.
In both groups, the prevalence of TTV viremia was higher among HIV-1–positive persons compared with those who were HIV-1 negative [33.3% (6/18) versus 12.4% (20/161) among IDUs (odds ratio [OR], 3.5; 95% CI, 1.0–11.5) and 7.8% (4/51) versus 3.0% (4/134) among MSM (OR, 2.8; 95% CI, 0.5–15.4)].
Among IDUs, TTV-DNA was significantly associated with older age and was marginally associated with longer duration of drug injection and of syringe sharing (data not shown). Among MSM, TTV-DNA was significantly associated with older age and longer duration of sexual activity (Table 1).
Transfusion-transmitted virus viremia was also significantly associated with a documented history of STDs, particularly gonorrhea. Seven of 72 (9.7%) MSM with a history of STDs were TTV-DNA positive, compared with 1 of 113 (0.9%) MSM with no history of STDs (OR, 10.5; 95% CI, 1.3–475.2). Four of 28 (14.3%) MSM with a history of gonorrhea were TTV-DNA positive, compared with 4 of 157 (2.5%) MSM with no history of gonorrhea (OR, 6.4; 95% CI, 1.1–36.1) (Table 1). The TTV-DNA also tended to be associated with a history of syphilis [4/48 (8.3%) versus 4/137 (2.9%); OR, 3.0; 95%CI, 0.5–16.8], though this association was not statistically significant. No association was found with a history of genital herpes [0/5 (0.0%) versus 8/180 (4.4%)] or genital warts [0/7 (0.0%) versus 8/178 (4.5%); OR, not calculable] (data not shown).
Previous studies have shown that TTV prevalence is generally higher among persons at risk of parenteral transmission and is associated with other parenterally transmitted viruses (i.e., HIV, hepatitis B and C virus). We also found a higher TTV prevalence among IDUs compared with MSM. However, the association between TTV and HIV in both MSWM and IDUs strongly suggests similar routes of transmission for these infections within these population groups (i.e., parenteral among IDUs and sexual among MSM).
In conclusion, our preliminary findings show that among MSM, TTV infection is associated with a longer duration of sexual exposure and a history of diseases caused by sexually transmitted agents. Therefore, it is likely that TTV is transmitted through sexual intercourse among MSM. The observed prevalence is lower among MSM compared with IDUs, possibly because the virus was introduced more recently among persons at risk for sexually transmitted infections, or because the efficiency of sexual transmission may be lower than that of parenteral transmission.
GIOVANNI REZZA, MD*
MAURO ZACCARELLI, MD†
MASSIMO GIULIANI, DSc*‡
SILVIA CALCATERRA, DSc†
ANNA ROSA GARBUGLIA, DSc†
CORRADO CATALANI, MD§
MARIA BENVENUTI, MD§
ALDO DI CARLO, MD†
GIUSEPPE IPPOLITO, MD† AND
ANDREA ANTINORI, MD†
1. Okamoto H, Nishizawa T, Kato N, et al. Molecular cloning and characterization of a novel DNA virus (TTV) associated with post-transfusion hepatitis of unknown etiology. Hepatol Res 1998; 10: 1–16.
2. Ikeda H, Takasu M, Inoue K, Okamoto H, Myakawa Y, Mayumi M. Infection with an unenveloped DNA virus (TTV) in patients with acute or chronic liver disease of unknown etiology and in those positive for hepatitis C virus RNA. J Hepatol 1999; 30: 205–212.
3. Simmonds P, Davidson F, Lycett C, et al. Detection of a novel DNA virus (TTV) in blood donors and blood products. Lancet 1998; 352: 191–195.
4. Desai SM, Muerhoff AS, Leary TP. Prevalence of TT Virus infection in US blood donors and populations at risk for acquiring parenterally transmitted viruses. J Infect Dis 1999; 179: 1242–1244.
5. MacDonald DM, Scott GR, Clutterbuck D, Simmonds P. Infrequent detection of TT virus infection in intravenous drug users, prostitutes, and homosexual men. J Infect Dis 1999; 179: 686–689.
6. Huang YH, Wu JC, Lin CC, et al. Prevalence and risk factor analysis of TTV infection in prostitutes. J Med Virol 2000; 60: 393–395.
7. Naoumov NV, Petrova EP, Thomas MG, Williams R. Presence of a newly described human DNA virus (TTV) in patients with liver disease. Lancet 1998; 352: 195–197.