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.
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.
BackgroundIn a malaria-endemic area the distribution of patients is neither constant in time nor homogeneous in space. The WHO recommends the stratification of malaria risk on a fine geographical scale. In the village of Cacao in French Guiana, the study of the spatial and temporal distribution of malaria cases, during an epidemic, allowed a better understanding of the environmental factors promoting malaria transmission.MethodsA dynamic cohort of 839 persons living in 176 households (only people residing permanently in the village) was constituted between January1st, 2002 and December 31st, 2007.The information about the number of inhabitants per household, the number of confirmed cases of Plasmodium vivax and house GPS coordinates were collected to search for spatial or temporal clustering using Kurlldorff’s statistical method.ResultsOf the 839 persons living permanently in the village of Cacao, 359 persons presented at least one vivax malaria episode between 2002 and 2007. Five temporal clusters and four spatial clusters were identified during the study period. In all temporal clusters, April was included. Two spatial clusters were localized at the north of the village near the Comté River and two others localized close to orchards.ConclusionThe spatial heterogeneity of malaria in the village may have been influenced by environmental disturbances due to local agricultural policies: deforestation, cultures of fresh produce, or drainage of water for agriculture. This study allowed generating behavioural, entomological, or environmental hypotheses that could be useful to improve prevention campaigns.
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