BackgroundCutaneous leishmaniasis (CL) is a disfiguring disease that confronts clinicians with a quandary: leave patients untreated or engage in a complex or toxic treatment. Topical treatment of CL offers a practical and safe option. Accordingly, the treatment of CL with WR279,396, a formulation of paromomycin and gentamicin in a hydrophilic base, was investigated in a phase 2 clinical study in Tunisia and France.MethodsA phase 2, randomized, double blind, vehicle-controlled study was conducted to assess the safety and efficacy of topical WR279,396 when applied twice a day for 20 days as treatment for parasitologically confirmed CL. The study protocol established the primary efficacy end point as complete clinical response (CCR) defined as 50% or greater reduction in the ulceration size of an index lesion by day 50 (D50) followed by complete re-epithelialization by D100, and no relapse through D180.ResultsNinety-two subjects were randomized. Leishmania major was identified in 66 of 68 isolates typed (97%). In the intent-to-treat population, 47 of 50 WR279,396 treated participants (94%) met the definition of CCR, compared with 30 of 42 vehicle-placebo participants (71%) [p = 0.0045]. Erythema occurred in 30% and 24% of participants receiving WR279,396 and placebo, respectively [p = 0.64]. There was no clinical or laboratory evidence of systemic toxicity.ConclusionApplication of WR279,396 for 20 days was found to be safe and effective in treating L. major CL, and offers great potential as a new, simple, easily applicable, and inexpensive topical therapy for this neglected disease.Trial RegistrationClinicalTrials.gov NCT00703924

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To investigate the association between HLA-DRB1* alleles and post-streptococcal acute glomerulonephritis (PSAGN) in Egyptian children, 32 unrelated patients with PSAGN and 380 healthy individuals from the same locality were typed for DRB1* alleles using the polymerase chain-reverse hybridization technique. Patients with PSAGN had significantly increased frequency of both DRB1* 03011 (46.9 vs. 19.2% in controls, P=0.00025) and DRB1* 1105 (31.1 vs. 15.6% in controls, P=0.0097) alleles. However, after correction of P values, only the difference for DRB1* 03011 allele remained significant (Pc=0.025). Their relative risks were significantly high (3.71, confidence interval [CI]=1.8-7.8, and 3.57, CI=1.4-8.9 respectively). No significant differences in the frequency of the two alleles were observed among patients with different grades of hypertension or proteinuria. In conclusion, DRB1* 03011, and possibly 1105, alleles confer susceptibility to PSAGN. However, the severity of the disease is not determined by these two alleles.

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Objectives To perform a systematic literature review and meta-analysis on endothelial cell (EC) markers that are involved and dysregulated in systemic lupus erythematosus (SLE) in relation to disease activity, as EC dysregulation plays a major role in the development of premature atherosclerosis in SLE. Methods Search terms were entered into Embase, MEDLINE, Web of Science, Google Scholar and Cochrane. Inclusion criteria were 1) studies published after 2000 reporting measurements of EC markers in serum and/or plasma of SLE patients (diagnosed according to ACR/SLICC criteria), 2) English language peer reviewed articles, and 3) disease activity measurement. For meta-analysis calculations, the Meta-Essentials tool by Erasmus Research Institute and of Management (ERIM) was used. Only those EC markers, which were 1) reported in at least two articles and 2) reported a correlation coefficient (i.e. Spearman’s rank or Pearson’s) between the measured levels of the EC marker and disease activity were included. For meta-analyses, a fixed effect model was used. Results From 2133 hits, 123 eligible articles were selected. The identified SLE-related endothelial markers were involved in EC activation, EC apoptosis, disturbed angiogenesis, defective vascular tone control, immune dysregulation and coagulopathy. Meta-analyses of primarily cross-sectional studies showed significant associations between marker levels and disease activity for the following endothelial markers: Pentraxin-3, Thrombomodulin, VEGF, VCAM-1, ICAM-1, IP-10 and MCP-1. Dysregulated EC markers without associations with disease activity were: Angiopoeitin-2, vWF, P-Selectin, TWEAK and E-Selectin. Conclusions We provide a complete literature overview for dysregulated EC markers in SLE comprising a wide range of different EC functions. SLE-induced EC marker dysregulation was seen with, but also without, association with disease activity. This study provides some clarity in the eminent complex field of EC markers as biomarkers for SLE. Longitudinal data on EC markers in SLE are now needed to guide us more in unravelling the pathophysiology of premature atherosclerosis and cardiovascular events in SLE patients.

This study shows, for the first time, natural Leishmania infection among Jaculus spp. in an endemic region of Tataouine, South Tunisia. To better characterize the transmission cycles in this complex focus of mixed transmission, Leishmania detection and species identification were performed by direct examination, internal transcribed spacer-1 (ITS1)-PCR-restriction fragment length polymorphism (RFLP), and sequencing of Jaculus (J.) jaculus (Linnaeus, 1758) and J. hirtipes (Lichtenstein, 1823) rodent species, which are frequently encountered in this area. Leishmania parasites were observed in 19 (41.3%) smears, while DNA parasites were detected in 28 (60.9%) Jaculus spp. spleens; among them, 12 (54.5%) were from 22 J. jaculus individuals and 16 (66.7%) were from 24 J. hirtipes individuals. Leishmania parasites were confirmed as Leishmania (L.) killicki (syn. L. tropica) in two J. hirtipes individuals (4.3%) and L. major (n = 24; 52.2%) in 10 J. jaculus and 14 J. hirtipes individuals. This finding represents the first evidence of natural infection with Leishmania parasites in rodents belonging to the Jaculus genus, providing the rationale to consider them as potential reservoir hosts of Old World Leishmania parasites in Tunisia and North Africa.

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Phlebotomine sandflies (Diptera: Psychodidae) constitute a large group of flies, many of which have been described as vectors of leishmaniasis, a disease caused by Leishmania (Kinetoplastida: Trypanosomatidae) parasites. In Tunisia, a total of 17 species belonging to both genera Phlebotomus and Sergentomyia were described. In this work we report on an abnormality found in spermathecae of a female specimen of Phlebotomus (Larroussius) longicuspis Nitzulescu, 1930. Sandflies were collected in SidiSaad locality, in the governorate of Kairouan, central Tunisia, where zoonotic cutaneous leishmaniasis is endemic, during the June to November 2011 period, using CDC light traps. Males were washed and directly identified and females were dissected and morphologically identified using the head and the last two abdominal segments containing spermathecae and ducts. 162 flies were morphologically described. Among 33 females identified as Phlebotomus (Larroussius) longicuspis, one specimen was found abnormal and presented with three spermathecae. An additional spermathecae located in a short bifurcation on the upper extremity of one duct was found. This anomaly is for the first time described in Tunisia. Morphological abnormalities are important to report in order to avoid erroneous sandfly identification or description of new species.