EthnoepidemiologyofAdultT-CellLeukemia/Lymphoma(Atl)andHuman
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EthnoepidemiologyofAdultT-CellLeukemia,Lymphoma(Atl)andHumanT-CellLeukemiaVirusTypeI(Htlv-I)
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Kazuo TAJIMA , MD , MPH, PhD
Director , Aichi Cancer Center Research Institute, Nagoya , JAPAN
Introduction
Human T-cell leukemia virus type (HTLV-I) (Poiesz et al, 1980; Hinuma et al, 1981) is the main causal agent of adult T-cell leukemia/lymphoma (ATL) (Uchiyama et al, 1977) and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) (Osame et al, 1986; Gessain et al, 1985) which are spread throughout the world, whereas HTLV type II (HTLV-II) (Kalyanaraman VS, 1982) is detected in very limited groups in America and Africa. The HTLV is enveloped virus with a diameter of 80-100 nm and its virion contains two covalently bound genomic RNA strands, which are combined with viral enzymes reverse transcriptase, integrase and protease and the capsid proteins (Yoshida et al, 1982). Two successive steps are generally necessary to demonstrate the presence of specific antibodies against HTLV-I and HTLV-II in serum (WHO, 1990). The first is screening assay which includes particle agglutination assay, enzyme-linked immunosorbent assay and immunofluorescence assay. The second confirmatory assays use western blot to confirm specific antibodies to HTLV-I or HTLV-II. Phylogenetically, three subtypes of HTLV-I, which were defined as groups of viral strains with common nucleotides at any provirus portion of DNA sequence, are assigned as the cosmopolitan, central African and Melanesian (Koralnik et al, 1994; Ido et al, 1996). HTLV-II are classified into two main subtypes as to IIa and IIb which are commonly found in drug users and American natives, respectively (Hall et al, 1992).
Based on strict confirmatory study of HTLV-I antibodies, highly endemic groups, as defined by high HTLV-I prevalence rates, include Mongoloids in Asia and South America, Negroids in tropical Africa, the Caribbean and as well as Atlantic coasts in South America, Australoids in Papua New Guinea and the north Australia (Tajima and Hinuma, 1992). The geographical distribution of HTLV-I is considered important evidence of the migration history of our ancestors from anthropological and ethnological point of view. The unique ethnic clusters of patients with HTLV-I associated diseases in the world could be explained by the natural history of familial transmission of HTLV-I which is limited via mother-to-child (breast feeding) and man-to-woman (sexual contact) (Tajima, 1996). The present study reviews the geographical and demographic distribution of HTLV-I, clinico-pathological features of ATL, its risk factors and essential preventive measures.
Ethnoepidemiologic Features of HTLV-I and Its Related Diseases
Macrogeographic distribution
In Africa , carriers of HTLV-I are clustered in the central and western tropical countries where HTLV-I carriers among general people ranged 0-20% (Tajima and Hinuma, 1992). Highly endemic areas were detected in southern Gabon (Delaporte et al, 1988) and northern Zaire (Goubau et al, 1993). On the other hand, less than 1% of the people showed positive for anti-HTLV-I antibody in northern Africa . HTLV-II is also endemic in specific Pygmy tribes from Zaire (Goubau et al, 1993) and Cameroon (Gessain et al, 1995). Most Europeans do not carry HTLV-I/II except for several white groups in southern Italy and Portugal . As shown in the Caribbean basin, immigrants from the Caribbean in London carry HTLV-I (Matutes et al, 1994).
In the Southeast Asian countries other than Japan , only a hunting-gathering people, the Aeta in the Philippines , show an extremely high rate of HTLV-I carriers (Ishida et al, 1988). A recent study showed that more than 10% of the Mashadi Jews in northern Iran carried the virus (Meytes et al, 1990). In other central Asian countries, sporadic distributions of HTLV-I carriers and patients with ATL were disclosed recently among Chinese on the east coast of China , Singapore , and Hong Kong, Koreans in Korea , Indians in Singapore and India , Jewish in Israel and Eskimo in Alaska (Tajima and Hinuma, 1992). We found no evidence of any HTLV-II clustering area and/or ethnic group in Asian countries.
HTLV-I carriers are widely distributed among Amerindian people who live along the Andes mountains from Colombia (Zaninovic et al, 1990) to Chile (Fujiyoshi et al, 1996). In the Andes of South America, carriers were found only among an isolated indigenous people living in a central hinterland located several hours by jeep from the center of a large city. A recent report suggests that HTLV-II is widely distributed among American natives from the Central America to the southern end of America (Tajima et al, 1995). As observed throughout the world, HTLV-I/II shows a geographical distribution that is linked to the modern history of human migration. For example, HTLV-I carriers are found among immigrant Japanese in Hawaii (Nomura et al, 1990) and Bolivia (Ohtsu et al, 1987), as well as among immigrant Africans in Central and South America (Blattner et al, 1983; Pombo de Oliveira et al, 1990).
Microgeographic distribution
According to evidence obtained from a biennial nationwide surveillance of ATL carried out in Japan since 1986, the annual incidence is estimated to be 700 from approximately 1.2 million HTLV-I carriers in Japan (Tajima et al, 1990). Those patients with ATL and HTLV-I carriers are found mainly in the southern and northern ATL endemic areas. Among 2,264 ATL cases newly diagnosed during the 6 years from 1990 to 1995 (The T- and B-cell Malignancy Study Group, 1998), 71% of the ATL patients were born in the southwestern districts of Kyushu and Shikoku, and 8.4% in the northern districts of Hokkaido and Tohoku. The geographical pattern of patients with HAM from two nationwide studies was very similar to that of ATL (Osame et al, 1994), and thus consistently related to that of HTLV-I carriers in this country.
The microgeographical distribution of HTLV-I carriers on an ATL endemic island of Japan mirrors that in Japan and the world. There were many HTLV-I carriers in places isolated from neighboring villages by steep and rocky forests and where people from different villages did not often visit each other because of the difficulty of transportation (Tajima et al, 1987). On the other hand, carriers were relatively few in each northernmost and southernmost village. The former had been a core village for cultural interchange between Japan and China since the 7-8th century and the latter was newly established about 100 years ago by many immigrants from districts outside of the ATL endemic areas. Because of the proximity of the low-rate village to the highly endemic villages, it is suggested that this virus does not spread easily under natural conditions.......（后略) ......
Kazuo TAJIMA , MD , MPH, PhD
Director , Aichi Cancer Center Research Institute, Nagoya , JAPAN
Introduction
Human T-cell leukemia virus type (HTLV-I) (Poiesz et al, 1980; Hinuma et al, 1981) is the main causal agent of adult T-cell leukemia/lymphoma (ATL) (Uchiyama et al, 1977) and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) (Osame et al, 1986; Gessain et al, 1985) which are spread throughout the world, whereas HTLV type II (HTLV-II) (Kalyanaraman VS, 1982) is detected in very limited groups in America and Africa. The HTLV is enveloped virus with a diameter of 80-100 nm and its virion contains two covalently bound genomic RNA strands, which are combined with viral enzymes reverse transcriptase, integrase and protease and the capsid proteins (Yoshida et al, 1982). Two successive steps are generally necessary to demonstrate the presence of specific antibodies against HTLV-I and HTLV-II in serum (WHO, 1990). The first is screening assay which includes particle agglutination assay, enzyme-linked immunosorbent assay and immunofluorescence assay. The second confirmatory assays use western blot to confirm specific antibodies to HTLV-I or HTLV-II. Phylogenetically, three subtypes of HTLV-I, which were defined as groups of viral strains with common nucleotides at any provirus portion of DNA sequence, are assigned as the cosmopolitan, central African and Melanesian (Koralnik et al, 1994; Ido et al, 1996). HTLV-II are classified into two main subtypes as to IIa and IIb which are commonly found in drug users and American natives, respectively (Hall et al, 1992).
Based on strict confirmatory study of HTLV-I antibodies, highly endemic groups, as defined by high HTLV-I prevalence rates, include Mongoloids in Asia and South America, Negroids in tropical Africa, the Caribbean and as well as Atlantic coasts in South America, Australoids in Papua New Guinea and the north Australia (Tajima and Hinuma, 1992). The geographical distribution of HTLV-I is considered important evidence of the migration history of our ancestors from anthropological and ethnological point of view. The unique ethnic clusters of patients with HTLV-I associated diseases in the world could be explained by the natural history of familial transmission of HTLV-I which is limited via mother-to-child (breast feeding) and man-to-woman (sexual contact) (Tajima, 1996). The present study reviews the geographical and demographic distribution of HTLV-I, clinico-pathological features of ATL, its risk factors and essential preventive measures.
Ethnoepidemiologic Features of HTLV-I and Its Related Diseases
Macrogeographic distribution
In Africa , carriers of HTLV-I are clustered in the central and western tropical countries where HTLV-I carriers among general people ranged 0-20% (Tajima and Hinuma, 1992). Highly endemic areas were detected in southern Gabon (Delaporte et al, 1988) and northern Zaire (Goubau et al, 1993). On the other hand, less than 1% of the people showed positive for anti-HTLV-I antibody in northern Africa . HTLV-II is also endemic in specific Pygmy tribes from Zaire (Goubau et al, 1993) and Cameroon (Gessain et al, 1995). Most Europeans do not carry HTLV-I/II except for several white groups in southern Italy and Portugal . As shown in the Caribbean basin, immigrants from the Caribbean in London carry HTLV-I (Matutes et al, 1994).
In the Southeast Asian countries other than Japan , only a hunting-gathering people, the Aeta in the Philippines , show an extremely high rate of HTLV-I carriers (Ishida et al, 1988). A recent study showed that more than 10% of the Mashadi Jews in northern Iran carried the virus (Meytes et al, 1990). In other central Asian countries, sporadic distributions of HTLV-I carriers and patients with ATL were disclosed recently among Chinese on the east coast of China , Singapore , and Hong Kong, Koreans in Korea , Indians in Singapore and India , Jewish in Israel and Eskimo in Alaska (Tajima and Hinuma, 1992). We found no evidence of any HTLV-II clustering area and/or ethnic group in Asian countries.
HTLV-I carriers are widely distributed among Amerindian people who live along the Andes mountains from Colombia (Zaninovic et al, 1990) to Chile (Fujiyoshi et al, 1996). In the Andes of South America, carriers were found only among an isolated indigenous people living in a central hinterland located several hours by jeep from the center of a large city. A recent report suggests that HTLV-II is widely distributed among American natives from the Central America to the southern end of America (Tajima et al, 1995). As observed throughout the world, HTLV-I/II shows a geographical distribution that is linked to the modern history of human migration. For example, HTLV-I carriers are found among immigrant Japanese in Hawaii (Nomura et al, 1990) and Bolivia (Ohtsu et al, 1987), as well as among immigrant Africans in Central and South America (Blattner et al, 1983; Pombo de Oliveira et al, 1990).
Microgeographic distribution
According to evidence obtained from a biennial nationwide surveillance of ATL carried out in Japan since 1986, the annual incidence is estimated to be 700 from approximately 1.2 million HTLV-I carriers in Japan (Tajima et al, 1990). Those patients with ATL and HTLV-I carriers are found mainly in the southern and northern ATL endemic areas. Among 2,264 ATL cases newly diagnosed during the 6 years from 1990 to 1995 (The T- and B-cell Malignancy Study Group, 1998), 71% of the ATL patients were born in the southwestern districts of Kyushu and Shikoku, and 8.4% in the northern districts of Hokkaido and Tohoku. The geographical pattern of patients with HAM from two nationwide studies was very similar to that of ATL (Osame et al, 1994), and thus consistently related to that of HTLV-I carriers in this country.
The microgeographical distribution of HTLV-I carriers on an ATL endemic island of Japan mirrors that in Japan and the world. There were many HTLV-I carriers in places isolated from neighboring villages by steep and rocky forests and where people from different villages did not often visit each other because of the difficulty of transportation (Tajima et al, 1987). On the other hand, carriers were relatively few in each northernmost and southernmost village. The former had been a core village for cultural interchange between Japan and China since the 7-8th century and the latter was newly established about 100 years ago by many immigrants from districts outside of the ATL endemic areas. Because of the proximity of the low-rate village to the highly endemic villages, it is suggested that this virus does not spread easily under natural conditions.......（后略) ......
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