Treatment of neuromyelitis optica with rituximab: a 2-year prospective multicenter study

International audienc

High circulating proviral load with oligoclonal expansion of HTLV-1 bearing T cells in HTLV-1 carriers with strongyloidiasis.

International audienceAdult 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 significantly 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 effect 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 five times higher in HTLV-1 carriers with strongyloidiasis than in HTLV-1+ individuals without Ss infection (P<0.009). 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 amplification of HTLV-1 flanking sequences. The positive effect of Ss on clonal expansion was reversible under effective treatment of strongyloidiasis in one patient with parasitological cure whereas no significant modification 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 - 496

Strongyloides stercoralis : global distribution and risk factors

The soil-transmitted threadworm, Strongyloides stercoralis, is one of the most neglected among the so-called neglected tropical diseases (NTDs). We reviewed studies of the last 20 years on S. stercoralis's global prevalence in general populations and risk groups.; A literature search was performed in PubMed for articles published between January 1989 and October 2011. Articles presenting information on infection prevalence were included. A Bayesian meta-analysis was carried out to obtain country-specific prevalence estimates and to compare disease odds ratios in different risk groups taking into account the sensitivities of the diagnostic methods applied. A total of 354 studies from 78 countries were included for the prevalence calculations, 194 (62.4%) were community-based studies, 121 (34.2%) were hospital-based studies and 39 (11.0%) were studies on refugees and immigrants. World maps with country data are provided. In numerous African, Asian and South-American resource-poor countries, information on S. stercoralis is lacking. The meta-analysis showed an association between HIV-infection/alcoholism and S. stercoralis infection (OR: 2.17 BCI: 1.18-4.01; OR: 6.69; BCI: 1.47-33.8), respectively.; Our findings show high infection prevalence rates in the general population in selected countries and geographical regions. S. stercoralis infection is prominent in several risk groups. Adequate information on the prevalence is still lacking from many countries. However, current information underscore that S. stercoralis must not be neglected. Further assessments in socio-economic and ecological settings are needed and integration into global helminth control is warranted

Coinfection by Strongyloides stercoralis in blood donors infected with human T-cell leukemia/lymphoma virus type 1 in São Paulo city, Brazil

The frequency of coinfection with Strongyloides stercoralis and human T-cell leukemia/lymphoma virus type 1 (HTML-1) was determined in 91 blood donors examined at the blood bank of a large hospital in São Paulo city, Brazil. As control group 61 individuals, not infected by HTLV-1, were submitted to the same techniques for the diagnosis of S. stercoralis infection. In HTLV-1 infected patients the frequency of S. stercoralis infection was 12.1%; on the other hand, the control group showed a frequency significantly lower of S. stercoralis infection (1.6%), suggesting that HTLV-1 patients shoud be considered as a high risk group for strongyloidiasis in São Paulo city

Strongyloidiasis and Infective Dermatitis Alter Human T Lymphotropic Virus-1 Clonality in vivo.

Human T-lymphotropic Virus-1 (HTLV-1) is a retrovirus that persists lifelong by driving clonal proliferation of infected T-cells. HTLV-1 causes a neuroinflammatory disease and adult T-cell leukemia/lymphoma. Strongyloidiasis, a gastrointestinal infection by the helminth Strongyloides stercoralis, and Infective Dermatitis associated with HTLV-1 (IDH), appear to be risk factors for the development of HTLV-1 related diseases. We used high-throughput sequencing to map and quantify the insertion sites of the provirus in order to monitor the clonality of the HTLV-1-infected T-cell population (i.e. the number of distinct clones and abundance of each clone). A newly developed biodiversity estimator called "DivE" was used to estimate the total number of clones in the blood. We found that the major determinant of proviral load in all subjects without leukemia/lymphoma was the total number of HTLV-1-infected clones. Nevertheless, the significantly higher proviral load in patients with strongyloidiasis or IDH was due to an increase in the mean clone abundance, not to an increase in the number of infected clones. These patients appear to be less capable of restricting clone abundance than those with HTLV-1 alone. In patients co-infected with Strongyloides there was an increased degree of oligoclonal expansion and a higher rate of turnover (i.e. appearance and disappearance) of HTLV-1-infected clones. In Strongyloides co-infected patients and those with IDH, proliferation of the most abundant HTLV-1(+) T-cell clones is independent of the genomic environment of the provirus, in sharp contrast to patients with HTLV-1 infection alone. This implies that new selection forces are driving oligoclonal proliferation in Strongyloides co-infection and IDH. We conclude that strongyloidiasis and IDH increase the risk of development of HTLV-1-associated diseases by increasing the rate of infection of new clones and the abundance of existing HTLV-1(+) clones

Two-Step Nature of Human T-Cell Leukemia Virus Type 1 Replication in Experimentally Infected Squirrel Monkeys (Saimiri sciureus)

After experimental infection of squirrel monkeys (Saimiri sciureus) with human T-cell leukemia virus type 1 (HTLV-1)-infected cells, the virus is transcribed only transiently in circulating blood, spleen, and lymph nodes. Stable disappearance of viral expression occurs at 2 to 3 weeks after inoculation. This coincides with the development of the anti-HTLV-1 immune response and persistent detection of the provirus in peripheral blood mononuclear cells (PBMCs). In this study, the HTLV-1 replication pattern was analyzed over time in PBMCs and various organs from two HTLV-1-infected squirrel monkeys. Real-time quantitative PCR confirmed that PBMCs and lymphoid organs constitute the major reservoirs for HTLV-1. The PCR amplification of HTLV-1 flanking sequences from PBMCs evidenced a pattern of clonal expansion of infected cells identical to that observed in humans. Dissemination of the virus in body compartments appeared to result from cellular transport of the integrated provirus. The circulating proviral burden increased as a function of time in one animal studied over a period of 4 years. The high proviral loads observed in the last samples resulted from the accumulation of infected cells via the extensive proliferation of a restricted number of persistent clones on a background of polyclonally expanded HTLV-1-positive cells. Therefore, HTLV-1 primary infection in squirrel monkeys is a two-step process involving a transient phase of reverse transcription followed by persistent multiplication of infected cells. This suggests that the choice of the target for blocking HTLV-1 replication might depend on the stage of infection