No abstract

Adult T cell leukemia (ATLL) develops in 3 ± 5% of HTLV-1 carriers after a long period of latency during which a persistent polyclonal expansion of HTLV-1 infected lymphocytes is observed in all individuals. This incubation period is signi®cantly shortened in HTLV-1 carrier with Strongyloides stercoralis (Ss) infection, suggesting that Ss could be a cofactor of ATLL. As an increased T cell proliferation at the asymptomatic stage of HTLV-1 infection could increase the risk of malignant transformation, the e ect of Ss infection on infected T lymphocytes was assessed in vivo in HTLV-1 asymptomatic carriers. After real-time quantitative PCR, the mean circulating HTLV-1 proviral load was more than ®ve times higher in HTLV-1 carriers with stongyloidiasis than in HTLV-1+ individuals without Ss infection (P50.009). This increased proviral load was found to result from the extensive proliferation of a restricted number of infected clones, i.e. from oligoclonal expansion, as evidenced by the semiquantitative ampli®-cation of HTLV-1¯anking sequences. The positive e ect of Ss on clonal expansion was reversible under e ective treatment of strongyloidiasis in one patient with parasitological cure whereas no signi®cant modi®cation of the HTLV-1 replication pattern was observed in an additional case with strongyloidiasis treatment failure. Therefore, Ss stimulates the oligoclonal proliferation of HTLV-1 infected cells in HTLV-1 asymptomatic carriers in vivo. This is thought to account for the shortened period of latency observed in ATLL patients with strongyloidiasis. Oncogene (2000) 19, 4954 ± 4960.

In order to gain new insights into the risk factors influencing human‐T‐cell‐leukemia/lymphoma‐virus‐type‐I (HTLV‐I) mother‐to‐child transmission, a retrospective study of HTLV‐I infection among children born to HTLV‐I‐seropositive women was carried out in a highly HTLV‐I‐endemic population of African origin living in French Guyana. The study covered 81 HTLV‐I‐seropositive mothers and their 216 children aged between 18 months old and 12 years old. All plasma samples were tested for the presence of HTLV‐I antibodies by ELISA, immunofluorescence assay and Western blot. HTLV‐I provirus was detected, in the DNA extracted from peripheral‐blood mononuclear cells, by polymerase chain reaction (PCR) using primers specific for 3 different HTLV‐I genomic regions (LTR, gag and pX) and quantified by a competitive PCR assay. Out of the 216 children, 21 were found to be HTLV‐I‐seropositive, giving a crude HTLV‐I transmission rate of 9.7%, while among the 180 breast‐fed children 10.6% were HTLV‐I‐seropositive. Perfect concordance between serological and PCR results was observed, and none of the 195 HTLV‐I‐negative children was found HTLV‐I‐positive by PCR. In conditional (by family) logistic‐regression models, HTLV‐I seropositivity in children was associated with an elevated maternal anti‐HTLV‐I‐antibody titer (OR 2.2, p = 0.0013), a high maternal HTLV‐I proviral load (OR 2.6, p = 0.033) and child's gender, girls being more frequently HTLV‐I‐infected than boys: OR 3.6, p = 0.0077 in the model including maternal anti‐HTLV‐I‐antibody titer and OR 4.1, p = 0.002 in the model including the maternal HTLV‐I proviral load. Int. J. Cancer 82:832–836, 1999. © 1999 Wiley‐Liss, Inc.

This work presents a method to find previously established relationships between drugs and adverse events in the literature. Using MEDLINE, following a MeSH approach to filter the signals, is a valid option. Our contribution is available as a web service that will be integrated in the final European EU-ADR project (Exploring and Understanding Adverse Drug Reactions by integrative mining of clinical records and biomedical knowledge) automated system.

To determine the epidemiological characteristics of human T cell leukemia/lymphoma virus type I (HTLV‐I) infection in the endemic village of Maripasoula, French Guiana, 1,614 persons (83.2% of the population) aged 2 to 91 years (mean age 21) were studied from November 1994 through April 1995. Plasma samples were screened by an HTLV‐I ELISA and an IFA test (on MT2 cells), and positive samples were tested by an HTLV‐I and ‐II type‐specific Western blot. Overall seropositivity in the village was 6.7%, but HTLV‐I infection was restricted to 3 of 6 ethnic groups, including the Noir‐Marron (descendants of escaped African slaves, 8%), the Creoles (4.1%) and those of mixed Noir Marron/other ethnicity (3.6%). In the Noir‐Marron population of 1,222 persons, including 606 men and 616 women and representing 76% of those tested, HTLV‐I seroprevalence increased significantly with age in both sexes, reaching 40% in women older than 50 years. Univariate risk factors for HTLV‐I seropositivity in women included older age, more pregnancies, more live births and a history of hospitalization. A cross‐sectional analysis of sexual partners demonstrated an excess of discordant female HTLV‐I+/male HTLV‐I− couples, indicating preferential male‐to‐female sexual transmission. The demonstration of 11 HTLV‐I‐seropositive children aged less than 15 years, of whom 9 had a seropositive mother, suggested maternal–child HTLV‐I transmission. Our results demonstrate a very high seroprevalence of HTLV‐I in this South American population descended from African slaves, probably due to high rates of mother‐to‐child and sexual transmission within this rather isolated group. Int. J. Cancer 76:331–336, 1998.© 1998 Wiley‐Liss, Inc.