Leishmania tarentolae expressing CXCL-10 as an efficient immunotherapy approach against Leishmania major-infected BALB/c mice.

Recent findings have demonstrated the suitability of interferon-gamma-induced protein 10 (IP-10) or CXCL-10 as an immunotherapy tool in treatment of leishmaniasis. This chemokine can overcome Leishmania (L.) infection through inducing nitric oxide (NO) production for parasite elimination. This study was undertaken to investigate the therapeutic effects of recombinant Leishmania tarentolae expressing CXCL-10 and an expression vector encoding CXCL-10 (pcDNA-CXCL-10-EGFP) in a model of BALB/c mice susceptible to infection by Leishmania major. The outcome of intervention was examined at 3 weeks post-treatment by evaluating the parameters of parasite burden (PB), arginase activity, NO and various cytokines such as IFN-γ, IL-4, IL-6 and IL-10. The results have shown that despite the efficacy of CXCL-10 expression vector as gene therapy, the live therapy strategy using L. tarentolae expressing CXCL-10 was more effective in terms of decreasing PB. Nitric oxide production increased, especially in the live therapy approaches. Arginase activity also decreased in all regimens, which demonstrates the potency of the treatment. The overall cytokine production shifted in favour of Th1 responses in the treated mice. Altogether, recombinant L. tarentolae expressing CXCL-10 represents a promising therapeutic strategy to improve treatment of cutaneous leishmaniasis.

Arginase activity of Leishmania isolated from patients with cutaneous leishmaniasis.

Cutaneous leishmaniasis (CL) is one of the most important vector-borne parasitic diseases, highly endemic in Iran, and its prevalence is increasing all over the country. Arginase (ARG) activity in isolated Leishmania parasites from CL patients is yet to be explored. This study aimed to compare the ARG activity of isolated Leishmania promastigotes from CL patients with a standard strain of Leishmania major and its influences on the disease pathogenesis. We recruited 16 confirmed CL patients from Qom Province, in central Iran; after detection of Leishmania species using PCR-RFLP, we assessed the levels of ARG in the isolated promastigotes and determined the parasites' growth rate. Only L. major was identified from CL patients. The level of ARG activity in the isolated Leishmania promastigotes from CL patients was significantly higher than that obtained from the standard strain of L. major. No significant correlations between ARG activity and lesion size, number or duration were observed; in contrast, a significant negative correlation was seen between ARG level and Leishmania' growth rate. The obtained results suggest that increased ARG expression and activity in the isolated Leishmania promastigotes might contribute to the higher parasite infectivity and play a major role in the pathogenicity of the CL.

Comparison of antigenemia assay and semiquantitative polymerase chain reaction test for monitoring active cytomegalovirus infection in allogeneic hematopoietic cell transplant recipients.

OBJECTIVES: We sought to compare the antigenemia assay and in-house semiquantitative polymerase chain reaction to monitor human cytomegalovirus infection after transplant in hematopoietic cell transplant recipients. MATERIALS AND METHODS: A pp65 antigen test for polymorphonuclear leukocytes and a semiquantitative polymerase chain reaction for whole blood were performed for 201 samples obtained from 26 hematopoietic cell transplant recipients over a 3-month surveillance period. RESULTS: Fourteen episodes of antigenemia positivity were detected in 7 patients in whom human cytomegalovirus DNA loads and pp65-positive cells ranged between < 102 to 2.96 x 104 copies/mL and 0-35/ 5 x 104 polymorphonuclear leukocytes, respectively. A significant correlation was detected between human cytomegalovirus DNA load and the antigenemia test. A receiver operating characteristic analysis determined 5000 copies/mL of human cytomegalovirus as the threshold value for initiation of ganciclovir therapy. CONCLUSIONS: Based on a comparison of the pp65 antigenemia assay, quantification of human cytomegalovirus DNA in whole blood can be used to guide clinical management of hematopoietic cell transplant recipients. This approach may have important advantages including superior sensitivity and efficient monitoring of preemptive therapy, allowing inclusion of kinetic criteria in clinical guidelines. Furthermore, a high human cytomegalovirus load among patients with grade II-IV acute graft-versus-host disease may indicate a high risk of human cytomegalovirus disease among hematopoietic cell transplant patients. Human cytomegalovirus reactivation must be monitored using more-sensitive assays such as real-time polymerase chain reaction.