Background: A small fraction of Human T cell Leukemia Virus type-1 (HTLV-I) infected subjects develop a severe form of myelopathy. It has been established that patients with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) show an exaggerated immune response when compared with the immunological response observed in HTLV-I asymptomatic carriers. In this study the immunological responses in HAM/TSP patients and in HTLV-I asymptomatic carriers were compared using several immunological assays to identify immunological markers associated with progression from infection to disease.

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High tumor necrosis factor-alpha (TNF alpha) levels were present in the serum of 24 of 28 active visceral leishmaniasis (VL) patients (142.9 +/- 113.9 pg/ml, mean +/- SD), whereas levels were not elevated in 26 of 30 patients with cryptic leishmanial infection (16 asymptomatic, 4 with self-healing subclinical infection, and 10 posttreatment VL cases). Serum TNF alpha levels were also not elevated in 15 normal volunteers (11.3 +/- 15.6 pg/ml) and in 10 patients with tegumentary leishmaniasis (19.1 +/- 10.8 pg/ml). Leishmanial infection of human monocyte-derived macrophages enhanced the basal TNF alpha production by these cells, and this effect was further potentiated by treatment with recombinant interferon-gamma. After effective treatment of VL patients, serum TNF alpha levels dropped rapidly (129 +/- 112 vs. 9 +/- 13 pg/ml in 10 days), even before clinical parameters such as spleen size or parasitism, white blood cell count, or levels of hemoglobin returned to normal values. On the other hand, patients unresponsive to treatment remained with elevated levels (276 +/- 69 vs. 155 +/- 71 pg/ml in 10 days). Thus, serum TNF alpha levels in VL patients are a good parameter to monitor in determining host response to therapy.

Development of neurological symptoms or signs occurred in up to 30% of asymptomatic subjects during 8 years of follow-up.

Lectins from eight leguminous seeds from the Diocleae tribe were compared to Concanavalin A (Con A), a well known T cell mitogen, on the stimulation of lymphocyte proliferation and Interferon gamma (IFN-gamma) production by peripheral blood mononuclear cells (PBMC) from normal volunteers. Lectins from Canavalia brasiliensis and Dioclea virgata induced the highest lymphocyte proliferation, both much higher than levels obtained with Con A, whereas lectins from Dioclea guianensis var. lasiophylla and from Canavalia bonariensis induced the lowest stimulation. Lectins from Dioclea rostrata, D. grandiflora, D. violacea and Cratylia floribunda induced intermediate levels of proliferation. The highest stimulation for IFN-gamma production was obtained with the lectin from D. rostrata, followed by those of C. floribunda and C. brasiliensis; only the lectins from D. virgata and C. bonariensis induced an IFN-gamma production lower than the one obtained by Con A-stimulation. Since all these legumes belong to the same tribe of C. ensiformis (Con A), and all are supposed to exhibit very similar lectins, it is interesting the high variation in the stimulation of lymphocyte proliferation. It is also noteworthy the dissociation between this parameter and IFN-gamma production in the case of D. virgata. A detailed analysis on the structure of such lectins, and their ligand sugars on lymphocyte surface is necessary to further explore such differences.

Background Does an intervention designed to foster patient-centered communication and shared decision making among GPs and their patients with poorly controlled type 2 diabetes mellitus reduce the level of HbA1c. Methods The DEBATE trial is a cluster-randomized controlled trial conducted in German primary care and including patients with type 2 diabetes mellitus having an HbA1c level of 8.0% (64 mmol/mol) or above at the time of recruitment. Data was measured before intervention (baseline, T0), 6–8 months (T1), 12–14 months (T2), 18–20 months (T3), and 24–26 months (T4) after baseline. Main outcome measure is the level of HbA1c. Results In both, the intervention and the control group the decline of the HbA1c level from T0 to T4 was statistically significant (− 0.67% (95% CI: − 0.80,-0.54%; p < 0.0001) and − 0.64% (95% CI: − 0.78, − 0.51%; p < 0.0001), respectively). However, there was no statistically significant difference between both groups. Conclusions Although the DEBATE trial was not able to confirm effectiveness of the intervention tested compared to care as usual, the results suggest that patients with poorly controlled type 2 diabetes are able to improve their blood glucose levels. This finding may encourage physicians to stay on task to regularly approach this cohort of patients. Trial registration The trial was registered at ISRCTN registry under the reference ISRCTN70713571 . Electronic supplementary material The online version of this article (10.1186/s12875-019-0977-9) contains supplementary material, which is available to authorized users.

Human T cell lymphotropic virus type 1 (HTLV-1) infection is associated with an exacerbated type 1 immune response and secretion of high levels of proinflammatory cytokines. In contrast, helminthic infection induces a type 2 immune response. In the present study, the cytokine profile in HTLV-1 carriers coinfected with helminths (Strongyloides stercoralis and/or Schistosoma mansoni) was compared with that in HTLV-1 carriers not coinfected with helminths. Levels of interferon (IFN)- gamma were higher in HTLV-1 carriers not coinfected with helminths than in HTLV-1 carriers coinfected with helminths (P<.05). The overall frequency of IFN- gamma -expressing CD8+ and CD4+ cells was decreased in HTLV-1 carriers coinfected with helminths (P<.05). The percentage of interleukin (IL)-5- and IL-10-expressing T cells in HTLV-1 carriers coinfected with helminths was higher than that in HTLV-1 carriers not coinfected with helminths (P<.05). Moreover, we found that the prevalence of helminthic infection was 7-fold higher in HTLV-1 carriers than in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (P<.05). These data show that helminthic infection decreases activation of type 1 cells, which may influence the clinical outcome of HTLV-1 infection.

SummaryHuman T lymphotropic virus-type 1 (HTLV-1) is the causal agent of the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), adult T cell leukaemia/lymphoma and infective dermatitis associated with HTLV-1 (IDH). Over-production of proinflammatory cytokines and an increase in HTLV-1 proviral load are features of HAM/TSP, but the immunological basis of IDH has not been established. In addition to severe cutaneous manifestations, the importance of IDH relies on the observation that up to 30% of children with IDH develop HAM/TSP in childhood and adolescence. In this study we determined the immune response in patients with IDH measuring interleukin (IL)-4, IL-5, IL-10, interferon (IFN)-g and tumour necrosis factor (TNF)-a levels as well as the HTLV-1 proviral load. Additionally, regulatory cytokines and anti-cytokines were added to cultures to evaluate the ability of these molecules to down-modulate TNF-a and IFN-g synthesis. HTLV-1 carriers and patients with HAM/TSP served as controls. TNF-a and IFN-g levels were higher in IDH than in HTLV-1 carriers. There was no difference in IFN-g and TNF-a concentrations in IDH and HAM/TSP patients. There was a tendency for higher IL-4 mRNA expression and immunoglobulin E (IgE) levels in IDH than in HTLV-1 carriers, but the difference did not reach statistical significance. The HTLV-1 proviral load was significantly higher in IDH patients than in HTLV-1 carriers. IDH is characterized by an exaggerated Th1 immune response and high HTLV-1 proviral load. The similarities between the immunological response in patients with IDH and HAM/TSP and the high proviral load observed in IDH provide support that IDH is a risk factor for development of HAM/TSP.