Vol. 21. No. 5 Printed in Great Britain
International Journal of Epidemiology © International Epktemiotogical Association 1992
HTLV among Israeli Intravenous Drug Abusers S MAAYAN/ M DAN," R MARLINK'AND Y M CHENtt
Of the four known human retroviruses, only HIV1 infection has been documented among Israeli IV drug abusers to date.1 Recently human T lymphotropic virus (HTLV1) infection was reported in Iraq and Israel2'3 and adult T cell leukaemia was documented in Jewish immigrants from Iran.4 Since most intravenous (IV) drug abusers in Israel are of Middle Eastern origin, we have investigated HTLV infection in a group of IV drug abusers in which HIV1 infection was documented. We describe the factors associated with exposure to HIV and HTLV.
that was tested in terms of mean age, origin, travel history or duration of drug abuse. HTLV Type 1 and Type 2 Antibody Tests 1) An inhouse Western Blot (WB) with HTLV1 virus antigens produced in HUT 102 cell line was used as previously described.5 Seropositivity was defined as the presence of antibody to gag pl9 or p24 and env gp46 or gp61/68, according to the Public Health Service criteria.6 2) Radioimmunoprecipitation (RIPA)7 was performed using MT2 cell lysate as an HTLV1 antigen source and MO cell lysate as an HTLV2 antigen source.8 Seropositivity was defined as bands in the gp46 and gp61/68 regions.6 3) An inhouse Western Blot assay using recombinant HTLV envelope proteins RPBI and RPIIB as antigens: RPBI contains amino acid 166-201 from HTLV1 exterior glycoprotein gp46. RPIIB contains amino acids 96-235 from HTLV2 exterior glycoprotein gp52.8 In addition, commercial synthetic peptide immunoassay9 was used according to manufacturer's instructions to evaluate further the results of the recombinant proteins.
METHODS Sera were collected during 1986-1987 from 400 consecutive IV drug abusers attending the single methadone clinic for the Tel Aviv area. All subjects were interviewed regarding their origin, drug abuse habits, sexual preferences, prostitution, travel and needle sharing abroad. Eight individuals (2%) were found to be HIV1 seropositive.1 Of the 400 specimens, 299 specimens, including the eight HIV1 seropositive specimens were available for further HTLV1, 2 and HIV2 antibody tests. In 101 specimens, insufficient amount of serum was available for HTLV testing. The group that was not tested did not differ from the group
H1V2 Antibody Test An inhouse Western blot using HIV2 infected HUT78 cell line was used as antigen source.10
* Department of Clinical Microbiology, Hadassah University Hospital, Jerusalem, Israel •• Infectious Diseases Unit, Wolfson Hospital, Holon, Israel * Department of Cancer Biology, Harvard School of Public Health, Boston, USA * Current address: Institute of Public Health, National Yong Ming Medical College, Taipei, Taiwan.
RESULTS Demographic characteristics of the cohort have been reported previously.' All participants were sexually active and none reported homosexual behaviour. 995
Downloaded from http://ije.oxfordjournals.org/ at University of California, San Fransisco on April 16, 2015
Maayan S (Department of Clinical Microbiology, Hadassah University Hospital, Jerusalem, Israel), Dan M, Marlink R and Chen Y M. HTLV among Israeli intravenous drug abusers. Internationa/Journal of Epidemiology 1992; 21: 995-997 Since human T lymphotropic virus (HTLV) infection was recently described in Israel and other Middle Eastern countries, we have investigated the presence of HTLV type 1 and type 2 in a group of 299 intravenous (IV) drug abusers who were seen at a large methadone clinic in the Tet Aviv area in 1986-1987. We found that 1.3% were seropositive to HTLV. Further testing revealed that HTLV1 was the only HTLV serotype. In addition, no coinfection HIV1/HTLV1 and no HIV2 infection were detected. Since all HTLV seropositives were bom in Middle Eastern countries, did not travel outside Israel and were not infected by HIV1 or by HTLV type 2, it is possible that the source of HTLV1 infection in that group was in an endemic reservoir of HTLV1 in Israel. The detection of HTLV1 among IV drug abusers and among other groups in Israel necessitates more extensive HTLV testing in at-risk populations.
9%
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
TABLE 1 Epidemiological characteristics of HIV I and HTLV I seropositive IV drug abusers
HIV seropositive No. = 8
HTLV seropositive No. = 4
/•value
30 + 3.2
31+2
NS
7
4
NS
6.4 + 5.4
9.5 + 5.1
NS
Travel to AIDS endemic area
7
0
P< 0.005
Needle sharing abroad
6
0
P < 0.005
Parameter
Mean age (years) Middle Eastern origin Duration of IV drug abuse
ages and drug abuse practices of the people infected by HIV1 and HTLV1, suggest a common risk factor for the viruses, e.g. contaminated needles. The lack of travel of the HTLV1 seropositive individuals to HIV1 endemic areas, points to the possibility that HTLV1 was acquired locally. Other findings support the following hypothesis about the lack of coinfection HIV/HTLV: although it may be due to the low overall prevalence of the viruses in this cohort, it may point to two different viral sources, such as an endemic source within Israel (HTLV1) versus an epidemic source from outside the country (HIV1). This lack of HIV/HTLV coinfection was also observed in some groups of IV drug abusers who reside in high prevalence areas for HIV1. In those areas, HTLV infection was found to be age dependent.12'13 The Findings in relation to the lack of HTLV2 infection are in contrast with recent reports from the US and Europe, employing the PCR technique, which suggest that the prevailing HTLV strain among IV drug users is HTLV2.13"17 This again raises the possibility that HTLV1 was acquired from an endemic focus within Israel rather than from outside the country. Endemic focus for HTLV1 has recently been described among Iranian Jews from Mashad who reside in Israel.3 In addition, sporadic cases of HTLV1 associated with adult T cell leukaemia were described in Israel,4 Iraq2 and northern Egypt.18 Based on our analysis, no definite statement can be made regarding the mode of transmission (sexual or by sharing needles) of HTLV in this cohort and more studies in non-IV drug abuse individuals and in other ethnic groups who originated in the Middle Eact are needed to clarify the endemicity of HTLV in Israel. A 1.3% HTLV1 infection rate in this group of IV drug abusers, coupled with a 12% HTLV seropositivity rate in Mashadi Jews in Israel3 calls for more extensive HTLV testing of individuals from Iran and among other Middle Eastern groups to establish the prevalence of this infection in Israel.
REFERENCES 1
DISCUSSION This report indicates that infection by HTLV1 without infection by HTLV2 or HIV2 was present among Israeli IV drug abusers in 1986-1987. The lack of HIV2 antibodies is in accordance with the epidemiology of HIV2 which is centred mainly in West African countries. 10 " The similarity of HTLV1 and HIV1 antibody prevalence (1.3% and 2% respectively) and the similar
2
3
4
5
Dan M, Rock M, Bar Shani S. Prevalence of antibodies to HIV among IV drug abusers in Israel—Association with travel abroad. Int J Epidemiol 1989; 18: 239-41. Dank S, Nolan P, Doherty J, Oarson J, Tedder R. HTLV1 infection in Iraq. Lancet 1990; 336: 1135-36. Meytes D, Schochat B, Lee H et al. Serological and molecular survey for HTLV1 infection in a high risk Middle Eastern group. Lancet 1990; 336: 1533-35. Sidi Y, Meytes D, Schochat B et al. Adult cell lymphoma in Israeli patients of Iranian origin. Cancer 1990; 65: 590-93. Lee T H, CoUgan J E, Homma T, McLane M F, Tachiban* N, Essex M. Human T-ceU leukemia vims associated membrane
Downloaded from http://ije.oxfordjournals.org/ at University of California, San Fransisco on April 16, 2015
Of the 299 individuals tested, four (1.3%) were seropositive to HTLV by Western Blot and radioimmunoprecipitation: all four had antibodies detected by HTLV WB and HTLV1 and HTLV2 RIPA. The samples were also positive to RPBI and by HTLV1 synthetic peptide immunoassay; they gave negative results with RPIIB or HTLV2 synthetic peptide assay. None of the four HTLV seropositive individuals had HIV1 antibodies and all the eight HIV1 seropositive people were seronegative to HTLV. The group of four HTLV seropositive individuals consisted of two males and two females; the latter two were prostitutes. This group did not differ significantly from the 295 HTLV seronegative individuals with regard to their mean age (31 years), heterosexual activity, geographical origin from Middle Eastern countries (Israel, Iraq, Morocco) and years of IV drug abuse. As compared with eight HIV1 seropositive individuals, the four HTLV1 seropositive people had similar characteristics except that they did not travel or inject drugs in AIDS endemic areas (P < 0.005; Table 1).
HTLV AMONG ISRAELI DRUG ABUSERS 13
14
15
16
17
18
Manca N, Caruso A, Bonfanti C et al. HTLV1 seroprevalence in AIDS patients and in HIVl seropositive and seronegative subjects at risk for AIDS in Northern Italy. Euro J Epidemiol 1989:5:37-41. Lee H, Swanson P, Shorty V S, Zack J A, Rosenblatt J D, Chen I S. High rate of HTLV2 infection in seropositive IV drug abusers in New Orleans. Science 1989; 244: 471-75. Zdla D, Mori L, Sala M et al. HTLV2 infection in Italian drug abusers. Lancet 1990; 336: 575-77. Rosenblatt J D, Plaeger Marshall S, Giorgi J V et al. A clinical, hematologic and immunologic analysis of 21 HTLV2 infected intravenous drug users. Blood 1990; 76: 409-17. Kwok S, Gallo D, Hanson C, McKinney N, Poiesz B, Sninsky J J. High prevalence of HTLV2 among IV drug abusers: PCR confirmation and typing. AIDS Res Hum Retroviruses 1990; 6: 561-65. El Farrash M A, Badr M F, Hawas S A et al. Sporadic carriers of human T lymphotrophk virus type I in Northern Egypt. Microbiol Immunol 1988; 32: 981-84.
(Revised version received April 1992)
Downloaded from http://ije.oxfordjournals.org/ at University of California, San Fransisco on April 16, 2015
antigen: Identity of the major antigens recognized following virus infection. Proc NatlAcad Sci (Wash) 1984; 81: 3856-60. 6 Licensure of screening tests for antibody to human T-tymphotropic virus type 1. MMWR 1988; 37: 736-40, 745-^7. 7 Miyoshi I, Kubonishi I, Yoshimoto S. Type C virus particles in a cord T cell line derived by co-cultivating normal cord leukocytes and human leukemia T cells. Nature 1981; 294: 770-71. 8 Chen Y M, Lee T H, Wiktor S Z « al. Type-specific antigens for serological discrimination of HTLV1 and HTLV2 infections. Lancet 1990; 336: 1153-55. 9 Hosein B, Fang C T, Wang C Y. Synthetic peptides to distinguish HTLV1 from HTLV2 infection. Abstract Th-8-13; International Retrovirus Conference, Montego Bay, Jamaica, 1991. 10 Barin F, M'Boup S, Denis F el al. Serological evidence for virus related to simian T Lymphotropic retroviruses III in residents of West Africa. Lancet 1985; 2: 1387-90. 11 Kanki P J, M'Boup Souleymane, Ricard D et al. Human T lymphotropic virus type 4 and the Human Immunodeficiency Virus in West Africa. Science 1987; 236: 827-31. 12 Lee H H, Weiss S H, Brown L S « al. Patterns of HIVl and HTLV1/2 in IV drug abusers from the middle Atlantic and central regions of the U.S. / Infect Dis 1990; 62: 347-52.
997
International Journal of Epidemiology © International Epktemiotogical Association 1992
HTLV among Israeli Intravenous Drug Abusers S MAAYAN/ M DAN," R MARLINK'AND Y M CHENtt
Of the four known human retroviruses, only HIV1 infection has been documented among Israeli IV drug abusers to date.1 Recently human T lymphotropic virus (HTLV1) infection was reported in Iraq and Israel2'3 and adult T cell leukaemia was documented in Jewish immigrants from Iran.4 Since most intravenous (IV) drug abusers in Israel are of Middle Eastern origin, we have investigated HTLV infection in a group of IV drug abusers in which HIV1 infection was documented. We describe the factors associated with exposure to HIV and HTLV.
that was tested in terms of mean age, origin, travel history or duration of drug abuse. HTLV Type 1 and Type 2 Antibody Tests 1) An inhouse Western Blot (WB) with HTLV1 virus antigens produced in HUT 102 cell line was used as previously described.5 Seropositivity was defined as the presence of antibody to gag pl9 or p24 and env gp46 or gp61/68, according to the Public Health Service criteria.6 2) Radioimmunoprecipitation (RIPA)7 was performed using MT2 cell lysate as an HTLV1 antigen source and MO cell lysate as an HTLV2 antigen source.8 Seropositivity was defined as bands in the gp46 and gp61/68 regions.6 3) An inhouse Western Blot assay using recombinant HTLV envelope proteins RPBI and RPIIB as antigens: RPBI contains amino acid 166-201 from HTLV1 exterior glycoprotein gp46. RPIIB contains amino acids 96-235 from HTLV2 exterior glycoprotein gp52.8 In addition, commercial synthetic peptide immunoassay9 was used according to manufacturer's instructions to evaluate further the results of the recombinant proteins.
METHODS Sera were collected during 1986-1987 from 400 consecutive IV drug abusers attending the single methadone clinic for the Tel Aviv area. All subjects were interviewed regarding their origin, drug abuse habits, sexual preferences, prostitution, travel and needle sharing abroad. Eight individuals (2%) were found to be HIV1 seropositive.1 Of the 400 specimens, 299 specimens, including the eight HIV1 seropositive specimens were available for further HTLV1, 2 and HIV2 antibody tests. In 101 specimens, insufficient amount of serum was available for HTLV testing. The group that was not tested did not differ from the group
H1V2 Antibody Test An inhouse Western blot using HIV2 infected HUT78 cell line was used as antigen source.10
* Department of Clinical Microbiology, Hadassah University Hospital, Jerusalem, Israel •• Infectious Diseases Unit, Wolfson Hospital, Holon, Israel * Department of Cancer Biology, Harvard School of Public Health, Boston, USA * Current address: Institute of Public Health, National Yong Ming Medical College, Taipei, Taiwan.
RESULTS Demographic characteristics of the cohort have been reported previously.' All participants were sexually active and none reported homosexual behaviour. 995
Downloaded from http://ije.oxfordjournals.org/ at University of California, San Fransisco on April 16, 2015
Maayan S (Department of Clinical Microbiology, Hadassah University Hospital, Jerusalem, Israel), Dan M, Marlink R and Chen Y M. HTLV among Israeli intravenous drug abusers. Internationa/Journal of Epidemiology 1992; 21: 995-997 Since human T lymphotropic virus (HTLV) infection was recently described in Israel and other Middle Eastern countries, we have investigated the presence of HTLV type 1 and type 2 in a group of 299 intravenous (IV) drug abusers who were seen at a large methadone clinic in the Tet Aviv area in 1986-1987. We found that 1.3% were seropositive to HTLV. Further testing revealed that HTLV1 was the only HTLV serotype. In addition, no coinfection HIV1/HTLV1 and no HIV2 infection were detected. Since all HTLV seropositives were bom in Middle Eastern countries, did not travel outside Israel and were not infected by HIV1 or by HTLV type 2, it is possible that the source of HTLV1 infection in that group was in an endemic reservoir of HTLV1 in Israel. The detection of HTLV1 among IV drug abusers and among other groups in Israel necessitates more extensive HTLV testing in at-risk populations.
9%
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
TABLE 1 Epidemiological characteristics of HIV I and HTLV I seropositive IV drug abusers
HIV seropositive No. = 8
HTLV seropositive No. = 4
/•value
30 + 3.2
31+2
NS
7
4
NS
6.4 + 5.4
9.5 + 5.1
NS
Travel to AIDS endemic area
7
0
P< 0.005
Needle sharing abroad
6
0
P < 0.005
Parameter
Mean age (years) Middle Eastern origin Duration of IV drug abuse
ages and drug abuse practices of the people infected by HIV1 and HTLV1, suggest a common risk factor for the viruses, e.g. contaminated needles. The lack of travel of the HTLV1 seropositive individuals to HIV1 endemic areas, points to the possibility that HTLV1 was acquired locally. Other findings support the following hypothesis about the lack of coinfection HIV/HTLV: although it may be due to the low overall prevalence of the viruses in this cohort, it may point to two different viral sources, such as an endemic source within Israel (HTLV1) versus an epidemic source from outside the country (HIV1). This lack of HIV/HTLV coinfection was also observed in some groups of IV drug abusers who reside in high prevalence areas for HIV1. In those areas, HTLV infection was found to be age dependent.12'13 The Findings in relation to the lack of HTLV2 infection are in contrast with recent reports from the US and Europe, employing the PCR technique, which suggest that the prevailing HTLV strain among IV drug users is HTLV2.13"17 This again raises the possibility that HTLV1 was acquired from an endemic focus within Israel rather than from outside the country. Endemic focus for HTLV1 has recently been described among Iranian Jews from Mashad who reside in Israel.3 In addition, sporadic cases of HTLV1 associated with adult T cell leukaemia were described in Israel,4 Iraq2 and northern Egypt.18 Based on our analysis, no definite statement can be made regarding the mode of transmission (sexual or by sharing needles) of HTLV in this cohort and more studies in non-IV drug abuse individuals and in other ethnic groups who originated in the Middle Eact are needed to clarify the endemicity of HTLV in Israel. A 1.3% HTLV1 infection rate in this group of IV drug abusers, coupled with a 12% HTLV seropositivity rate in Mashadi Jews in Israel3 calls for more extensive HTLV testing of individuals from Iran and among other Middle Eastern groups to establish the prevalence of this infection in Israel.
REFERENCES 1
DISCUSSION This report indicates that infection by HTLV1 without infection by HTLV2 or HIV2 was present among Israeli IV drug abusers in 1986-1987. The lack of HIV2 antibodies is in accordance with the epidemiology of HIV2 which is centred mainly in West African countries. 10 " The similarity of HTLV1 and HIV1 antibody prevalence (1.3% and 2% respectively) and the similar
2
3
4
5
Dan M, Rock M, Bar Shani S. Prevalence of antibodies to HIV among IV drug abusers in Israel—Association with travel abroad. Int J Epidemiol 1989; 18: 239-41. Dank S, Nolan P, Doherty J, Oarson J, Tedder R. HTLV1 infection in Iraq. Lancet 1990; 336: 1135-36. Meytes D, Schochat B, Lee H et al. Serological and molecular survey for HTLV1 infection in a high risk Middle Eastern group. Lancet 1990; 336: 1533-35. Sidi Y, Meytes D, Schochat B et al. Adult cell lymphoma in Israeli patients of Iranian origin. Cancer 1990; 65: 590-93. Lee T H, CoUgan J E, Homma T, McLane M F, Tachiban* N, Essex M. Human T-ceU leukemia vims associated membrane
Downloaded from http://ije.oxfordjournals.org/ at University of California, San Fransisco on April 16, 2015
Of the 299 individuals tested, four (1.3%) were seropositive to HTLV by Western Blot and radioimmunoprecipitation: all four had antibodies detected by HTLV WB and HTLV1 and HTLV2 RIPA. The samples were also positive to RPBI and by HTLV1 synthetic peptide immunoassay; they gave negative results with RPIIB or HTLV2 synthetic peptide assay. None of the four HTLV seropositive individuals had HIV1 antibodies and all the eight HIV1 seropositive people were seronegative to HTLV. The group of four HTLV seropositive individuals consisted of two males and two females; the latter two were prostitutes. This group did not differ significantly from the 295 HTLV seronegative individuals with regard to their mean age (31 years), heterosexual activity, geographical origin from Middle Eastern countries (Israel, Iraq, Morocco) and years of IV drug abuse. As compared with eight HIV1 seropositive individuals, the four HTLV1 seropositive people had similar characteristics except that they did not travel or inject drugs in AIDS endemic areas (P < 0.005; Table 1).
HTLV AMONG ISRAELI DRUG ABUSERS 13
14
15
16
17
18
Manca N, Caruso A, Bonfanti C et al. HTLV1 seroprevalence in AIDS patients and in HIVl seropositive and seronegative subjects at risk for AIDS in Northern Italy. Euro J Epidemiol 1989:5:37-41. Lee H, Swanson P, Shorty V S, Zack J A, Rosenblatt J D, Chen I S. High rate of HTLV2 infection in seropositive IV drug abusers in New Orleans. Science 1989; 244: 471-75. Zdla D, Mori L, Sala M et al. HTLV2 infection in Italian drug abusers. Lancet 1990; 336: 575-77. Rosenblatt J D, Plaeger Marshall S, Giorgi J V et al. A clinical, hematologic and immunologic analysis of 21 HTLV2 infected intravenous drug users. Blood 1990; 76: 409-17. Kwok S, Gallo D, Hanson C, McKinney N, Poiesz B, Sninsky J J. High prevalence of HTLV2 among IV drug abusers: PCR confirmation and typing. AIDS Res Hum Retroviruses 1990; 6: 561-65. El Farrash M A, Badr M F, Hawas S A et al. Sporadic carriers of human T lymphotrophk virus type I in Northern Egypt. Microbiol Immunol 1988; 32: 981-84.
(Revised version received April 1992)
Downloaded from http://ije.oxfordjournals.org/ at University of California, San Fransisco on April 16, 2015
antigen: Identity of the major antigens recognized following virus infection. Proc NatlAcad Sci (Wash) 1984; 81: 3856-60. 6 Licensure of screening tests for antibody to human T-tymphotropic virus type 1. MMWR 1988; 37: 736-40, 745-^7. 7 Miyoshi I, Kubonishi I, Yoshimoto S. Type C virus particles in a cord T cell line derived by co-cultivating normal cord leukocytes and human leukemia T cells. Nature 1981; 294: 770-71. 8 Chen Y M, Lee T H, Wiktor S Z « al. Type-specific antigens for serological discrimination of HTLV1 and HTLV2 infections. Lancet 1990; 336: 1153-55. 9 Hosein B, Fang C T, Wang C Y. Synthetic peptides to distinguish HTLV1 from HTLV2 infection. Abstract Th-8-13; International Retrovirus Conference, Montego Bay, Jamaica, 1991. 10 Barin F, M'Boup S, Denis F el al. Serological evidence for virus related to simian T Lymphotropic retroviruses III in residents of West Africa. Lancet 1985; 2: 1387-90. 11 Kanki P J, M'Boup Souleymane, Ricard D et al. Human T lymphotropic virus type 4 and the Human Immunodeficiency Virus in West Africa. Science 1987; 236: 827-31. 12 Lee H H, Weiss S H, Brown L S « al. Patterns of HIVl and HTLV1/2 in IV drug abusers from the middle Atlantic and central regions of the U.S. / Infect Dis 1990; 62: 347-52.
997
