Case Report: Possible Links between Sickle Cell Crisis and Pentavalent Antimony

For over 60 years, pentavalent antimony (Sbv) has been the first-line treatment of leishmaniasis. Sickle cell anemia is a disease caused by a defect in red blood cells, which among other things can cause vasooclusive crisis. We report the case of a 6-year-old child with leishmaniasis who during treatment with meglumine antimoniate developed a sickle cell crisis (SCC). No previous reports describing the relationship between antimonial drugs and sickle cell disease were found. Reviews of both the pathophysiology of SCC and the mechanism of action of Sbv revealed that a common pathway (glutathione) may have resulted in the SCC. ChemoText, a novel database created to predict chemical-protein-disease interactions, was used to perform a more expansive and systematic review that was able to support the association between glutathione, Sbv, and SCC. Although suggestive evidence to support the hypothesis, additional research at the bench would be needed to prove Sbv caused the SCC

Regulatory T Cells in the Pathogenesis and Healing of Chronic Human Dermal Leishmaniasis Caused by Leishmania (Viannia) Species

The immune inflammatory response is a double edged sword. During infectious diseases, regulatory T cells can prevent eradication of the pathogen but can also limit inflammation and tissue damage. We investigated the role of regulatory T cells in chronic dermal leishmaniasis caused by species of the parasite Leishmania that are endemic in South and Central America. We found that although individuals with chronic lesions have increased regulatory T cells in their blood and at skin sites where immune responses to Leishmania were taking place compared to infected individuals who do not develop disease, their capacity to control the inflammatory response to Leishmania was inferior. However, healing of chronic lesions at the end of treatment was accompanied by an increase in the number and capacity of regulatory T cells to inhibit the function of effector T cells that mediate the inflammatory response. Different subsets of regulatory T cells, defined by the expression of molecular markers, were identified during chronic disease and healing, supporting the participation of distinct regulatory T cells in the development of disease and the control of inflammation during the healing response. Immunotherapeutic strategies may allow these regulatory T cell subsets to be mobilized or mitigated to achieve healing

El elipsoide tórico como cuerpo de referencia para la tomografía corneal

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Cirugía. Fecha de lectura: 13-11-2020Esta tesis tiene embargado el acceso al texto completo hasta el 13-05-202

Treg frequency and function increase after treatment of CDL.

<p>Frequency of cells with a Treg phenotype in PBMCs and suppressive capacity of CD4⁺CD25⁺ cells were determined for CDL patients (n = 11) before and after treatment. <b>A</b>. Frequency of CD4⁺CD25^hiFoxp3⁺ cells. <b>B</b>. Frequency of CD4⁺CD25^hiCD127⁻ cells. <b>C</b>. Frequency of CD4⁺CD25^hiGITR⁺ cells. <b>D</b>. Inhibition of CD4⁺CD25⁻ cell proliferation by CD4⁺CD25⁺ cells at a 1∶1 ratio after stimulation with <i>L. panamensis (L.p.)</i> and APCs. <b>E</b>. Inhibition of CD4⁺CD25⁻ cell proliferation by CD4⁺CD25⁺ cells at a 4∶1 ratio after stimulation with PHA. <b>F</b>. Inhibition of CD4⁺CD25⁻ cell IFN-γ secretion by CD4⁺CD25⁺ cells at a 1∶1 ratio after stimulation with <i>L.p.</i> and APCs. Inhibition was calculated only for subjects that had proliferation and IFN-γ levels above the average+2SD of control wells from the same co-culture (n = 10 for proliferation and 11 for IFN-γ secretion with <i>L.p.</i> stimulation and n = 11 for PHA stimulation). *p<0.05, paired t-test, **p<0.01, Wilcoxon signed-rank test.</p

IL-10 does not mediate suppression of effector functions by CD4⁺CD25⁺ cells.

<p>IL-10 was measured in supernatants from the CD4⁺CD25⁻-CD4⁺CD25⁺ co-cultures by ELISA. The level of IL-10 in the absence (1∶0 ratio) or presence (1∶1 ratio) of CD4⁺CD25⁺ cells is shown for AI (n = 6), CDL patients before treatment (n = 14), CDL patients after treatment (n = 11) and all co-cultures combined (n = 31). **p<0.01, Wilcoxon signed-rank test. Means with SEM are shown.</p

CDL patients have a higher frequency of CD4⁺CD25^hiFoxP3^<b>+</b> cells in peripheral blood than AI.

<p>PBMCs from AI (n = 12) and CDL patients (n = 14) were stained for CD4, CD25 and either Foxp3, CD127, or GITR and analyzed by flow cytometry. <b>A</b>. Frequency of CD4⁺CD25^hiFoxp3⁺ cells. <b>B</b>. Frequency of CD4⁺CD25^hiCD127⁻ cells. <b>C</b>. Frequency of CD4⁺CD25^hiGITR⁺ cells. ***p<0.001, Mann-Whitney test. The median is represented by a horizontal line.</p

Relative expression of <i>IDO</i> decreases in CDL patients after treatment and is correlated with <i>IFNG</i>.

<p>RNA was isolated from biopsies of lesions from CDL patients (n = 11) before and after treatment and the expression of <i>FOXP3</i> (<b>A</b>), <i>IFNG</i> (<b>B</b>), <i>IL10</i> (<b>C</b>) and <i>IDO</i> (<b>D</b>) was measured by qRT-PCR. The expression of each gene relative to healthy skin of four normal controls was calculated using the ΔΔCT method. <b>E</b>. Correlation between the relative expression of <i>IDO</i> and <i>FOXP3</i> (left panel) or <i>IFNG</i> (right panel). *p<0.05, Wilcoxon signed-rank test.</p

Clinical characteristics and evolution of chronic dermal leishmaniasis patients.

a<p>% of surface area of ulcer(s) or plaque(s) healed or volume of nodule(s) reduced at the end of treatment; ND: not determined because culture was not necessary or no strain was obtained; NA: not applicable.</p

Noninferiority of miltefosine versus meglumine antimoniate for cutaneous leishmaniasis in children

Q1Q1684-692BACKGROUND: Children have a lower response rate to antimonial drugs and higher elimination rate of antimony (Sb) than adults. Oral miltefosine has not been evaluated for pediatric cutaneous leishmaniasis. METHODS: A randomized, noninferiority clinical trial with masked evaluation was conducted at 3 locations in Colombia where Leishmania panamensis and Leishmania guyanensis predominated. One hundred sixteen children aged 2-12 years with parasitologically confirmed cutaneous leishmaniasis were randomized to directly observed treatment with meglumine antimoniate (20 mg Sb/kg/d for 20 days; intramuscular) (n = 58) or miltefosine (1.8-2.5 mg/kg/d for 28 days; by mouth) (n = 58). Primary outcome was treatment failure at or before week 26 after initiation of treatment. Miltefosine was noninferior if the proportion of treatment failures was ≤15% higher than achieved with meglumine antimoniate (1-sided test, α = .05). RESULTS: Ninety-five percent of children (111/116) completed follow-up evaluation. By intention-to-treat analysis, failure rate was 17.2% (98% confidence interval [CI], 5.7%-28.7%) for miltefosine and 31% (98% CI, 16.9%-45.2%) for meglumine antimoniate. The difference between treatment groups was 13.8%, (98% CI, -4.5% to 32%) (P = .04). Adverse events were mild for both treatments. CONCLUSIONS: Miltefosine is noninferior to meglumine antimoniate for treatment of pediatric cutaneous leishmaniasis caused by Leishmania (Viannia) species. Advantages of oral administration and low toxicity favor use of miltefosine in children