Variant Human T-cell Lymphotropic Virus Type 1c and Adult T-cell Leukemia, Australia

Lloyd Einsiedel¹

, Olivier Cassar¹, Peter Bardy, Daniel Kearney, and Antoine Gessain

Author affiliations: Flinders University/Northern Territory Rural Clinical School, Alice Springs, Northern Territory, Australia (L. Einsiedel); Institut Pasteur, Paris, France (O. Cassar, A. Gessain); Centre National de la Recherche Scientifique Unité Mixte de Recherche 3569, Paris (O. Cassar, A. Gessain); Royal Adelaide Hospital and Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia (P. Bardy, D. Kearney)

Abstract

Human T-cell lymphotropic virus type 1 is endemic to central Australia among Indigenous Australians. However, virologic and clinical aspects of infection remain poorly understood. No attempt has been made to control transmission to indigenous children. We report 3 fatal cases of adult T-cell leukemia/lymphoma caused by human T-cell lymphotropic virus type 1 Australo-Melanesian subtype c.

The human T-cell lymphotropic virus type 1 (HTLV-1) currently infects at least 5–10 million persons worldwide; however, this oncogenic retrovirus is not ubiquitous, and areas of high endemicity are typically separated by areas where infection is uncommon (1). Although 4 major molecular subtypes in specific geographic areas have been described, epidemiologic and clinical associations have been best documented for the HTLV-1a subtype, which predominates in the Caribbean region and Japan. Among HTLV-1 carriers in these regions, adult T-cell leukemia/lymphoma (ATLL) will ultimately develop in 1%–5% (2). Few clinical details are available with regard to infection with the Australo-Melanesian HTLV-1c subtype, which is restricted to impoverished indigenous populations in Australia and the neighboring islands of Oceania.
In Australia, HTLV-1 carriers were first reported among indigenous residents of remote desert communities in 1988 (3). The sole published HTLV-1 nucleotide sequence from an indigenous Australian belongs to the Australo-Melanesian HTLV-1c subtype (4). Genetic characterization of the few available HTLV-1c subtype strains indicates that they are relatively divergent compared with the Cosmopolitan HTLV-1a prototype. Within the env gene and long terminal repeat regions, for example, 7%–10% divergence has been demonstrated at the nucleotide level (5,6). Background prevalence rates among indigenous central Australian adults are thought to be from 7.2% through 13.9% (7,8). However, among those admitted to the only regional hospital, the seropositivity rate approaches 40% (8), and rates are even higher among patients > 45 years of age (49.3% for men; 38.5% for women) (8). The predominant mode of transmission among indigenous Australians is thought to be through breast-feeding (8).
In other populations, early acquisition of HTLV-1 infection is associated with an increased risk for ATLL (2). High HTLV-1 prevalence rates in some indigenous Australian and Melanesian communities coupled with frequent early childhood infection with HTLV-1 should therefore be associated with a correspondingly high risk for ATLL, yet few cases of HTLV-1–associated complications have been reported from Australasia (9,10). Indeed, the clinical significance of HTLV-1 infection in Australia has been questioned, and no attempt has been made to control virus transmission among the indigenous population (8). We report 3 cases of ATLL in indigenous Australian patients at the Alice Springs Hospital, central Australia, in 2002 and 2010. Case-patients 1 and 3 (Aus-NR and Aus-GJ) originated from the same community, ≈450 km from case-patient 2 (Aus-GM).