A SEROEPIDEMIOLOGICAL SURVEY OF HTLV-I/II CARRIERS IN THE PUNA JUJEÑA

JOSE EDGARDO DIPIERRI1, KATZUO TAJIMA2, LUIS CARTIER ROBIROSA3, SHUNRO SONODA4

1 Instituto de Biología de la Altura, Universidad Nacional de Jujuy, Argentina; 2 División of Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan; 3 Departamento de Neurología Clínica, Universidad de Chile, Santiago, Chile;
4 Department of Virology, Faculty of Medicine, Kagoshima University, Japan

Key words: HTLV-I/II, Puna Jujeña, seroepidemiology

Abstract

Human T-cell leukemia virus type I (HTLV-I) carriers are clustered in limited groups in the world. One of these groups is the Andean native population of South America. As part of an international collaborative study devoted to explore the clustering of HTVL-I carriers in different countries, the aim of this paper was to evaluate the seroprevalence of HTLV-I/II virus in the native population of Puna Argentina in Jujuy. Blood samples of individuals of three populations of Puna Jujeña (Susques, Rinconada, Cochinoca) were screened with particle agglutination (PA), immunofluorescence (IF) and western immunoblotting analysis (WB) tests. Two out 86 (2.32%) individuals examined in the Puna Jujeña showed positive results for HTLV-I antibodies. It is concluded that the Province of Jujuy, in particular its less miscegenated highest altitude areas, constitute the northern and southern Andean natural geographical clustering of HTLV-I. This distribution is probably linked both to a history of prehistoric human dispersal in the Andes and to high mother- to- child transmission of the virus under close conditions of each group.

Resumen

Estudio seroepidemiológico de portadores de HTLV-I/II en la Puna Jujeña. Los portadores del virus de la leucemia humana a células T tipo I (HTLV-I) se agrupan en determinados grupos en el mundo. Uno de estos grupos en Sudamérica es la población nativa de los Andes. Como parte de un estudio colaborativo internacional orientado a explorar la distribución de portadores HTLV-I en diferentes países, el propósito de este trabajo fue evaluar la seroprevalencia del virus HTLV-I/II en la población nativa de la Puna Argentina en la Provincia de Jujuy. Las muestras sanguíneas de individuos de tres poblaciones de la Puna Jujeña (Susques, Rinconada, Cochinoca) fueron analizadas con las siguientes pruebas: aglutinación de partículas (PA), inmunofluorescencia (IF) y western-blot (WB). De los 86 individuos examinados 2 (2.32%) presentaron anticuerpos de HTLV-I. Se concluye que la Provincia de Jujuy, y en particular sus áreas de altura menos miscegenizadas, forman parte del agrupamiento geográfico natural norte y surandino del virus HTLV-I. Esta distribución probablemente se encuentra ligada tanto a la dispersión humana prehistórica en los Andes como a una elevada transmisión del virus de madre a hijo propia de las condiciones de aislamiento de estos grupos.

Postal address: Dr. José Edgardo Dipierri, Bolivia 2335, 4600 San Salvador de Jujuy, Argentina. Fax: (54-388) 422-1597 E-mail: dipierri@inbial.unju.edu.ar

Received: 5-VII-1999 Accepted: 16-IX-1999

Human T-cell leukemia virus type I (HTVL-I) is the etiological agent for adult T-cell lymphoma/leukemia (ATL) and HTVL-I associated myelopathy (HAM)/tropical spastic paraparesis (TSP)1, 2. Human T-cell leukemia virus type I (HTVL-I) was found in an ATL cell line in the United States in 19803 and independently in Japan, in 19814. A related virus to HTVL-I was isolated from the transformed T cell of a patient with hairy cell leukemia and consequently this virus has been called HTLV type II to distinguish it from HTLV-I5.
The geographical distribution of HTLV-I and HTLV-II as well as the molecular epidemiological knowledge about this virus has been considered very useful in elucidating the present and past geographical distribution of various ethnic groups6. HTLV-I and HTLV-II carriers are clustered among limited groups in the world: Japanese and other minority groups in Asia, Blacks in Central Africa and the Caribbean basin, Melanesians in Papua New Guinea and Amerindians in Central and South America6. In America it was revealed that HTLV-I carriers are widely distributed among Amerindian people who live along the Andes range, from Colombia to Chile7. A recent report suggested that HTLV-II is naturally distributed among some American native groups living in the Atlantic coast, Gran Chaco and Amazonia7, 8, 9.
As part of an international collaborative study between Japan and Chile devoted to explore the clustering of HTVL-I carriers in both countries the aim of this paper was to evaluate the seroprevalence of HTLV-I/II virus in the neighbouring native population of Puna Argentina in Jujuy.

Populations and Methods

Four clearly defined geographic and ecological regions exist in Jujuy Province and collectively they constitute an altitudinal gradient with populations situated between 350 and 4.000 meters above sea level. One of these regions is Puna Jujeña, which comprises approximately 60% of the provincial territory, with an average altitude of 3.500 m. It is relatively sparsely settled where existing conditions are the most extreme within the high altitude environment. In its ethnic composition the contribution of the autochthonous predominates. In the prehispanic period these populations belonged to a set of ethnic groups: Atacama, Omaguacas, etc10. From a cultural point of view, these populations may be ascribed to the north-western cultural area of Argentina, a part of the Andean macro area10.
The sample consisted of individuals of both sexes (32 males; 54 females), randomly selected, coming from three towns in the Puna Jujeña: Susques (N = 40), Rinconada (N = 28) and Cochinoca (N = 18). Total populations in these three towns are 671, 369 and 400 respectively. We screened for antibodies to HTLV-I in sera by the gelatin particle agglutination test (PA test: Serodia HTLV-I Fujirebio, Tokyo). Sera positive in the PA test (titer < 16) were re-tested for immunofluorescence on MT-1 cells (IF test) and antibody specificity was confirmed by western immunoblotting analysis (WB test; Fujirebio). To detect the provirus DNA of HTLV-I and II in peripherical blood, PCR was performed as described elsewhere12. The primer set amplified the R and U5 regions of the LTR of HTLV-I (452 bp) and II (498 bp).

Results and Discussion

Two out of 86 (2.32%) persons (Table 1) examined in the Puna Jujeña showed positive for HTLV-I antibodies in the PA test and with the confirmation test (Fig. 1).
There are antecedents at national level13, 14, 15 of studies on seroprevalence of HTVL-I/II virus blood donation centers located in Buenos Aires, the capital city of the country (Table 2), the largest of which provided percentages of seropositive results below 0.5%. These percentages increase in patients under risk of horizontal or vertical transmission of HTLV-I/II virus: patients under hemodialisis, hemophiliacs, and intravenous hard drug consumers16. Studies on blood donors have also shown that the most prevalent virus was HTLV-I, and that most positive donors would come from the northern part of the country, with a strong Amerindian ethnic component, in particular from Jujuy and Formosa15.
The first case of TSP/HTLV-I was detected in Jujuy in 198917. Since then over 20 patients with this pathology have been studied. This information, added to serologic surveys made to date on blood donors (Table 1), suggest that the Province of Jujuy would be an endemic zone for virus HTLV-I16, 17, 18. However seroprevalence values in Jujenean blood donors are lower than that one found in this study (Table 1). The latter is similar to HTLV-I seropositivity rates found among highland populations of Jujuy Province18. These, in turn, are alike to those detected in amerindian people, biologically and culturally related to Jujenean populations, living along the Andes mountains from Colombia to Chile19: a) Aymara blood donors living in Bolivian altiplano (2.3%)20; b) north Chile Amerindians of San Pedro de Atacama (4.2%))7; c) Andean Amerindians from Colombia (3.9%)21.
It is concluded that the Province of Jujuy and in particular its less miscegenated regions of high altitude, would integrate the northern and southern Andean natural geographical clustering of HTLV-I, and that this distribution is probably linked both to a history of prehistoric human dispersal in the Andes and to high mother-to-child transmission of the virus under close conditions of each groups.

Acknowledgements: The authors wish to thank Dr. G. Alvarez, Director of the Maimará Hospital, and the Sanitary Station corresponding to the surveyed localities, as well as the APS staff members, for their invaluable contribution without which this study would not have been possible.

References

1. Gessain A, Barin F, Vernant JC. Antibody to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis. Lancet 1985; 2: 407-9.
2. Osame M, Usuku K, Izumo S. HTLV-I associated myelopathy, a new clinical entity. Lancet 1986; 1: 1031-2.
3. Poiesz BJ, Ruscetti FW, Gazda AF, Bunn PA, Minna JD, Gallo RC. Detection and isolation of type-C retrovirus particles from fresh and cultured lymphocytes of patients with cutaneous T-cell lymphoma. Proc Natl Acad Sci 1980; 77: 7415-9.
4. Hinuma Y, Nagata K, Hanaoka M, et al. Adult T-cell leukemia: Antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proc. Natl Acad Sci 1981; 78: 6476-80.
5. Kalyraranaman VS, Sarngadharan MG, Robert-Guroff M, et al. A new subtype of human T-cell leukemia virus (HTLV-II) associated with a T-cell variant of hairy cell leukemia. Science 1982; 218: 571-3.
6. Tajima K. HTLV-I/II related disease with special reference to its distribution among mongoloids. In: Ethnoepidemiology of cancer. Tajima K, Sonoda S, (eds). Gann Monograph on Cancer Research 1996; 44: 123-35.
7. Tajima K, Cartier L. Epidemiological features of HTLV-I and adult T cell leukemia. Intervirology 1995; 38: 238-46.
8. Zaninovic V, Sanzon F, Lopez F. Geographic indepen-dence of HTLV-I and HTLV-II foci in the Andes Highland, the Atlantic Coast, and the Orinoco of Colombia. AIDS Res Hum Retrovirus 1994; 10: 97-101.
9. Ferrer JF, Del Pino N, Esteban E, et al. High rates of infec-tion with human T-cell leukemia retrovirus type II in four in-dians populations of Argentina. Virology 1993; 197: 576-84.
10. Dipierri JE, Alfaro E, Bejarano IF. El patrimonio biológico de la Provincia de Jujuy. XUXUY Revista de Ciencia y Tecnología (UNJU) 1997; 2: 13-21.
11. Cartier L, Araya F, Castillo JL, et al. Southernmost carriers of HTLV-I/II in the world. Jpn J Can Res 1993; 84: 1-3.
12. Saiki RK, Gelfand DH, Stoffel S, et al. Primer-direct enzymatic amplification of DNA with a thermostable DNA polymerase. Science 1988; 239: 487-91.
13. Bouzas MB, Muchinik G, Zapiola I. HTLV-I/II in Argentina. IV. Conference on Retrovirology HTLV. Montego Bay, Jamaica, 1991.
14. Del Pino N, Martinez Peralta L, Pampurro S, Pimentel E, Libonatti O. HTLV-I/II seroprevalence and coinfection with other pathogens in blood donors in Buenos Aires. J Acquir Inmune Def Syndr 1994; 7: 206-7.
15. Zapiola EM, Muchinik G, Bouzas MB, Gioseffi O. Epidemiological features of positive HTLV-I/II blood donors from Buenos Aires, Argentina. Eighth International Conference on Human Retrovirology: HTLV. Rio de Janeiro, 1997.
16. Biglioni M. Epidemiology of HTLV-I and HTLV-II in South America. In: Zaninovic W. HTLV truths and questions, Fundación Mar, Editorial Cpcienciencia, Bogotá, Colombia. 1996; pp. 51-65.
17. Pintado A, Gastaldo S, Musri S, Remondegui C. HTLV-I prevalence in blood banks of Jujuy northwestern Argentina. Eighth International Conference on Human Retrovirology: HTLV. Rio de Janeiro, 1997.
18. Severich I, Gómez Pasqualini A, Pizarro M, Dipierri JE, Biglione M. Seroepidemiología del virus HTLV-I/II en la Provincia de Jujuy. Rev Arg Transf 1998; 24: 281-5.
19. Tajima K, Takezi T. Human T. Cell Leukemia virus Type I. Cancer Survey 1998; 33: 191-211.
20. Hurtado LV, Gomez LH, Andrade R, et al. HTLV-I infection and disease in Bolivian population. Eighth International Conference on Human Retrovirology: HTLV. Rio de Janeiro, 1997.
21. Fujiyoshi T, Zaninovic V, Cartier L, et al. Genetic segregation of HTLV-I and HTLV-II carriers among South American natives. AIDS Res Hum Retrovir 1994; 10: 486-90.

TABLE 1.– Reactivity of synthetic peptides derived from HTLV-I/II by PA and WB test in 2 out of 86 indigenous people in the Puna Jujeña

HTLV-I
Serodia HTLV-I HTLV-I/II western-blot
Sample Sex Age PA titers HTLV-I HTLV-II

ARG-009 F 30 X32 + -
SA7-38 F 29 X256 + -

TABLE 2.– HTLV-I/II seroprevalence in bank blood donors of different cities in Argentina

City Detection N° subjects Positives % Reference
methods HTLV-I HTLV-II

Buenos Aires IF/PCR 1.100 1 (0.09) 1 (0.09) 13
Buenos Aires IF/PA/WB 12.891 6 (0.05) 3 (0.02) 14
Buenos Aires IF/PA 13.481 9 (0.06) 3 (0.02) 15
S. S. de Jujuy PA/ELISA 4.805 39 (0.81) - 17
S. S. de Jujuy PA/IF 16.668 221 (1.19) - 18

Fig. 1.– Western blot patterns of representative cases of HTLV-I and HTLV-II carriers in South America. HTLC-I PC and HTLV-II PC are HTLV-I and HTLV-II positive control, respectively. NC is negative control. Lanes 1-6 are HTLV-I positive samples: lane 1; Aymara (CRM-41) in Bolivia, lanes 2-4; Atacama in North Chile (CHI-399, CHI-413 and CHI-444), lanes 5-6; Puna in North Argentina (ARG-009 and SA7-38). Lanes 7-16 are HTLV-II positive samples: lanes 7-14 correspond to Alacalfes (PE-001, PE-004 and PE-015), Yaganes (NA-001), Guahibo (2C-013, 2C-032, 2C-036 and 2C-055) respectively and lanes 15-16; Kayapo (KY66 and KY74).