Local Heat Application for the Treatment of Buruli Ulcer: Results of a Phase II Open Label Single Center Non Comparative Clinical Trial.

BACKGROUND Buruli ulcer (BU) is a necrotizing skin disease most prevalent among West African children. The causative organism, Mycobacterium ulcerans, is sensitive to temperatures above 37°C. We investigated the safety and efficacy of a local heat application device based on phase change material. METHODS In a phase II open label single center noncomparative clinical trial (ISRCTN 72102977) under GCP standards in Cameroon, laboratory confirmed BU patients received up to 8 weeks of heat treatment. We assessed efficacy based on the endpoints 'absence of clinical BU specific features' or 'wound closure' within 6 months ("primary cure"), and 'absence of clinical recurrence within 24 month' ("definite cure"). RESULTS Of 53 patients 51 (96%) had ulcerative disease. 62% were classified as World Health Organization category II, 19% each as category I and III. The average lesion size was 45 cm(2). Within 6 months after completion of heat treatment 92.4% (49 of 53, 95% confidence interval [CI], 81.8% to 98.0%) achieved cure of their primary lesion. At 24 months follow-up 83.7% (41 of 49, 95% CI, 70.3% to 92.7%) of patients with primary cure remained free of recurrence. Heat treatment was well tolerated; adverse effects were occasional mild local skin reactions. CONCLUSIONS Local thermotherapy is a highly effective, simple, cheap and safe treatment for M. ulcerans disease. It has in particular potential as home-based remedy for BU suspicious lesions at community level where laboratory confirmation is not available. CLINICAL TRIALS REGISTRATION ISRCT 72102977

TO SALT ADAPTATION OF OSTRACODA AND BRANCHIOPODA. THE MORPHOFUNCTIONAL, ECOLOGICAL AND EVOLUTION ASPECTS WITH SPECIAL CONSIDERATION OF REPRESENTATIVES OF THESE CRUSTACEOUS OF THE AREAL SEA

The purpose of the work: the revealation of osmotic relations of hemolymph and water, mechanisms of osmoregulation, the peculiarities of embryonal development and ecdysis, the effect of temperature and composition of salts, the variation of biovariety, depending on the factor of salting. The salt adaptations of 132 species have been studied, the morpho-functional, ecological and evoluation aspects have been analyzed. The methods of determination of the paleogalliness have been improved. The new organs of osmoregulation have been described. The data can be used for the determination of plaeogalliness, ecological monitoring and prognosis of the salt lakesecosystems development, and at compiling the plans of preservation and reablement of the Aral Sea. The results of the investigations have been used in preparation of diagnostic documents YNEP, YNESCO, World bankAvailable from VNTIC / VNTIC - Scientific & Technical Information Centre of RussiaSIGLERURussian Federatio

Localisation of large clusters of AFB in the subcutis of BU lesions.

<p>Histological sections were stained with ZN (counterstain methylenblue). A: Cross sections through the excised tissue specimens from BU plaque lesions (A2-A4, A7-A8) or ulcerated BU lesions (A1, A5-A6) revealing large clusters of AFB located in the subcutis in different tissue depths (3 mm—10 mm). Boxed areas are shown in a higher magnification in (B). B: Large clusters of AFB. C: High magnification of AFB with typical rod shaped appearance.</p

Correlation between direct smear microscopy and IS2404 qPCR results.

<p>Of the 123 IS2404 qPCR positive swab samples analyzed by direct smear microscopic analysis after ZN staining, 54 samples (43.9%) were only positive by qPCR, whereas 69 samples (56.1%) were positive for both methods applied. Up to a qPCR CT of 27.8 all swabs were positive for both methods. Between CT 27.9 and CT 33.8 results were variable and above CT 33.8 all samples were microscopy negative. A: AFB positive and negative swabs in correlation to the qPCR values. Each dot represents one swab sample. B: Percentage of AFB positive and negative swabs in correlation to qPCR value ranges.</p

Examples of lesions presenting with both IS2404 qPCR positive and negative swabs.

<p>Lesions of six laboratory confirmed BU patients are shown, whereof four (# 1–4) presented with a ∆CT value ≤ 10, indicating a minimal to medium heterogeneity and two (# 5 and 6) presented with a ∆CT value > 10, indicative for a maximum heterogeneity. From each lesion four swabs have been taken in a clockwise manner and IS2404 qPCR has been performed.</p

Increase in the probability of obtaining one or more positive qPCR results with the number of swabs analyzed.

<p>Increase in the probability of obtaining one or more positive qPCR results with the number of swabs analyzed.</p

Preferential location of <i>M</i>. <i>ulcerans</i> bacteria in the subcutis.

<p>A: In plaque lesions mainly large clusters of extracellular bacteria were found, whereas in ulcerated lesions single AFB and small clusters were more common. In both types of lesions AFB were primarily found in the subcutis. B: Examples for dispersed single bacteria (1) and small clusters of AFB (2) in histological sections stained with ZN (counterstain methylenblue).</p