BackgroundIn human leishmaniasis Th1/Th2 dichotomy similar to murine model is not clearly defined and surrogate marker(s) of protection is not yet known. In this study, Th1/Th2 cytokines (IL-5, IL-10, IL-13 and IFN-γ) profile induced by purified CD4+/CD8+ T cells in response to Leishmania antigens were assessed at transcript and protein levels in 14 volunteers with a history of self-healing cutaneous leishmaniasis (HCL) and compared with 18 healthy control volunteers.Methodology/Principal FindingsCD4+/CD8+/CD14+ cells were purified from peripheral blood using magnetic beads; CD4+/CD8+ T cells were co-cultured with autologous CD14+ monocytes in the presence of soluble Leishmania antigens (SLA). Stimulation of either CD4+ T cells or CD8+ T cells of HCL volunteers with SLA induced a significantly (P<0.05) higher IFN-γ production compared with the cells of controls. Upregulation of IFN-γ gene expression in CD4+ cells (P<0.001) and CD8+ cells (P = 0.006) of HCL volunteers was significantly more than that of controls. Significantly (P<0.05) higher fold-expression of IFN-γ gene was seen in CD4+ cells than in CD8+ cells. In HCL volunteers a significantly (P = 0.014) higher number of CD4+ cells were positive for intracellular IFN-γ production than CD8+ cells.Conclusions/SignificanceCollectively, the volunteers have shown maintenance of specific long-term immune responses characterized by a strong reaction to leishmanin skin test and IFN-γ production. The dominant IFN-γ response was the result of expansion of both CD4+ and CD8+ T cells. The results suggested that immune response in protected individuals with a history of zoonotic cutaneous leishmaniasis (ZCL) due to L. major is mediated not only through the expansion of antigen-specific IFN-γ producing CD4+ Th1 cells, but also through IFN-γ producing CD8+ T cells.

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The present data show the importance of CL as a health problem in suburban areas of Qom Province. In order to identify other epidemiological aspects of leishmaniasis in this area, studies on vectors and reservoirs are recommended. Since leishmaniasis caused by L. major is typically zoonotic, control measures should focus on rodents as the main reservoirs and Phlebotomus papatasi as the main vector. Awareness should be raised in the high-risk populations comprising people with diabetes, young adults (<25 years old), and those who work outdoors during the summer.

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Background: Trichomonas vaginalis (T.vaginalis) and Neisseria gonorrhoeae (N.gonorrhoeae) are two most common non-viral sexually transmitted infections in the world. No data are available regarding the epidemiology of genital infections in women of Qom, central Iran. Objective:Epidemiological investigation of sexually transmitted infections in genital specimens of women referred to the referral gynecology hospital in Qom, central Iran.Materials and Methods:Genital swab specimens were collected from women volunteers and used for identification of bacterial and protozoal infections by conventional microbial diagnostics, porA pseudo gene LightCycler® real-time PCR (for N.gonorrhoeae) and ITS-PCR (for T.vaginalis). Results:Of 420 volunteers, 277 (65.9%) had genital signs/symptoms, including 38.3% malodorous discharge, 37.9% dyspareunia, and 54.8% abdominal pain. Totally, 2 isolates of Streptococcus agalactiae were identified. Five specimens (1.2%) in Thayer-Martin culture and 17 (4.1%) in real-time PCR were identified as N.gonorrhoeae. Fifty-four specimens (12.9%) in wet mount, 64 (15.2%) in Dorset’s culture, and 81 (19.3%) in ITS-PCR showed positive results for T.vaginalis. Five mixed infections of T.vaginalis+ N.gonorrhoeae were found. The risk of T.vaginalis infection was increased in women with low-birth-weight (p=0.00; OR=43.29), history of abortion (p=0.00; OR=91.84), and premature rupture of membranes (PROM) (p=0.00; OR=21.75). The probability of finding nuclear leukocytes (p=0.00; OR=43.34) in vaginal smear was higher in T.vaginalis infection.Conclusion:The significant prevalence of trichomoniasis and gonorrhea emphasizes the need for accurate diagnosis and effective surveillance to prevent serious reproductive complications in women.

A combination of Leishmania-reactive IFN-γ producing CD4(+)CD45RO(+)CD45RA(-)CCR7(-) T(EM) and Leishmania-reactive IL-2 producing CD4(+)CD45RO(+)CD45RA(-)CCR7(+) T(CM) are identified in individuals with history of CL which might play a role in protective recall immune response against Leishmania infection.

The role of tumour necrosis factor-alpha (TNF-α) is not fully understood in human leishmaniasis. We analysed the alterations in the levels of TNF-α, soluble TNF receptor type 1 (sTNFR I), IL-17 and IL-22 productions in active and healed leishmaniases. Blood samples were collected from volunteers with active cutaneous leishmaniasis (ACL), the same subjects after lesion healing (healed CL = HCL), volunteers with active visceral leishmaniasis (AVL), healed VL (HVL) and healthy controls. Levels of cytokines were titrated on Leishmania Ag-stimulated PBMC culture. The mean level of TNF-α production from stimulated cells was significantly higher in ACL than controls (P < 0·001) and significantly reduced after treatment in HCL volunteers (P < 0·05). The mean level of sTNFR I production was significantly higher in ACL than controls (P < 0·001) and significantly reduced after treatment in HCL volunteers (P < 0·05). The mean level of IL-22 production in AVL was significantly higher than controls (P < 0·05) and was significantly lower in HVL compared with AVL (P < 0·001) and controls (P < 0·05). The levels of TNF-α (P = 0·0025) and sTNFR I (P < 0·01) productions from PBMCs showed significant decreasing trend after treatment in each CL volunteer. Reduction in TNF-α is associated with clinical response to treatment and healing of CL lesions due to L. major.

Clinical trials of killed Leishmania vaccines showed a limited efficacy compared with leishmanization (LZ). The reason for this difference in protection against cutaneous leishmaniasis (CL) is not known and in vivo studies on T-cell function may provide valuable information. Nevertheless, there are limited studies on the nature of the stimulatory effects of live vs. killed parasites on human T cells in vitro. A total of nine Leishmanin Skin Test+ volunteers with a history of self-healing CL (HCL) and seven healthy volunteers were included in this study. 5,6-carboxyfluroescein diacetate succinimidyl ester-labelled CD4(+)/CD8(+) lymphocytes were cultured with killed Leishmania Lysate (Killed LL) or live Leishmania major (Live LM) and analysed for proliferation using flow cytometry. Culture supernatants were used for cytokine titration. In HCL volunteers, upon stimulation with killed LL, the number of proliferated CD4(+)/CD8(+) cells was significantly more than that of unstimulated (P < 0.001) or live LM stimulated (P < 0.05) cells, or cells from controls (CD4(+)/CD8(+): P < 0.05/P < 0.001). Stimulation of CD4(+) cells with Live LM (P < 0.001) or Killed LL (P < 0.05) induced a significantly higher IFN-gamma production compared with that of controls, but Live LM induced significantly (P < 0.05) more IFN-gamma than Killed LL. A significantly (P < 0.05) higher IFN-gamma production was observed when CD8(+) cells were stimulated with Live LM. Cells from HCL volunteers showed significantly more IL-10 production to Live LM stimulation compared with that of controls (CD4(+): P < 0.05 /CD8(+): P < 0.001) or cells stimulated with Killed LL (CD4(+)/CD8(+): P < 0.001/P < 0.0005). Whereas Killed LL induced more proliferation response in purified T cells, Live LM induced cytokine production without significant induction of proliferation. The results from healed CL volunteers in this study could be implicated in further studies on T-cell response in vaccinated individuals.