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The relationship between strongyloidiasis and HTLV-I was investigated in Okinawa, an area where both conditions are endemic. Thirty-six patients with strongyloidiasis were seropositive for HTLV-I and suffered from several related clinical complications. Fourteen of these patients (39%) were shown to have monoclonal integration of HTLV-I proviral DNA in their blood lymphocytes, a condition designated as "smouldering" adult T-cell leukaemia (ATL). Monoclonal integration of proviral DNA correlated with an increased CD4/CD8 ratio and the presence of abnormal lymphocytes in the peripheral blood, and with a trend for greater severity of the parasitic infection. Although the immunodeficiency caused by HTLV-I could predispose to hyperinfestation by Strongyloides, it is also possible that both the parasitic and the retroviral infestations are important co-factors leading to the development of ATL.

The intermediate state of HTLV-1 infection, often found in individuals dually infected with Strongyloides stercoralis (S. stercoralis) and HTLV-1, is assumed to be a preleukemic state of adult T-cell leukemia (ATL). To investigate the e ects of S. stercoralis superinfection on the natural history of HTLV-1 infection, we characterized peripheral blood samples of these individuals in Okinawa, Japan, an endemic area for both HTLV-1 and S. stercoralis and we studied e ects of the parasite antigen on T-cells. The dually infected individuals showed a signi®cantly higher provirus load and an increase in CD4 + 25 + T cell population, with a signi®cant, positive correlation. This increase was attributable to polyclonal expansion of HTLV-1-infected cells, as demonstrated by inverse-long PCR analysis of the integration sites. S. stercoralis antigen activated the IL-2 promoter in reporter gene assays, induced production of IL-2 by PBMC in vitro, and supported growth of IL-2 dependent cell lines immortalized by HTLV-1 infection or the transduction of Tax. Taken collectively, these results indicate that S. stercoralis infection induces polyclonal expansion of HTLV-1-infected cells by activating the IL-2/IL-2R system in dually infected carriers, an event which may be a precipitating factor for ATL and in¯ammatory diseases.

We have studied 15 individuals (aged 14-74 years) with antibodies to HTLV-I in their serum and random integration of HTLV-I proviral DNA in their peripheral blood lymphocytes. All but one of these patients suffered from a variety of non-specific complaints which did not correspond to those of adult T-cell leukemia (ATL). All of them were born in Kyushu and Okinawa which are endemic areas for HTLV-I infection; 25% of their family members were also seropositive for HTLV-I. The only haematological abnormality in these patients was the presence of few atypical lymphoid cells in the peripheral blood. The CD4/CD8 ratios were normal but the proportion of Tac positive cells was slightly higher than normal. These individuals with polyclonal integration of HTLV-I proviral DNA seem to represent an intermediate state between smouldering ATL (monoclonal integration) and healthy HTLV-I carriers (with antibodies but no detectable HTLV-I proviral DNA). Patients with this intermediate state of HTLV-I infection may be at risk to progress to ATL. The natural history of HTLV-I infection in humans leading to the development of ATL is reviewed in the light of these new findings.

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