Prediction Score for Antimony Treatment Failure in Patients with Ulcerative Leishmaniasis Lesions

The manuscript is relevant because of the finding of a new risk factor for chemotherapy failure and the development of a prognosis score for cutaneous leishmaniasis. The proportion of patients that have multiple lesions in American Tegumentary Leishmaniasis (ATL) is considerable. Publications and our experience permit to estimate that they represent around 20% of the affected population from the Amazon basin with cutaneous lesions. In addition, about 1/3 of them would correspond to the concomitant distant lesions category, the novel risk factor identified with a very high odds ratio (20–30) associated. Such numbers merit study of concomitant distant ulcers category on its own, not only because of clinical management implications, but also to search for factors that are contributing to chemotherapy failure. Finally, the simple equation proposed in the manuscript can be easily adapted to smart phone technologies. Similar prognosis equations are scarce for other pathologies and do not exist for Cutaneous Leishmaniasis at all. The simplicity of this tool should be followed by subsequent epidemiologic studies in other ATL endemic regions

Microparticles as additives for increasing the mechanical stiffness of polypropylene

Composite materials of polypropylene and mineral microparticles have been generated by compounding and tested in terms of mechanical stiffness. In a first step silica, boehmite and functionalized clay microparticle powder have been mixed with the polymer in a twin-screw compounder. The elastic modulus was highest for mixtures with a microparticle concentration of 5 to 10%w/w. An increase of 25% of the elastic modulus was achieved by simple melt extrusion. In a second step, a maleic anhydride-grafted polypropylene (PP-g-MA) was used as a matrix. When measured by nanoindentation, the pure PP-g-MA matrix showed an elastic modulus twice as high as pure PP, probably because of a partial reticulation. During extrusion, amino-silane functionalized clay microparticles were added to the PP-g-MA matrix and reacted with it by building covalent amide group bonds. The resulting compound material showed an elastic modulus of more than four times the stiffness of pure PP

Burden of visceral leishmaniasis in villages of eastern gedaref state, Sudan: an exhaustive cross-sectional survey.

Since December 2009, Médecins Sans Frontières has diagnosed and treated patients with visceral leishmaniasis (VL) in Tabarak Allah Hospital, eastern Gedaref State, one of the main endemic foci of VL in Sudan. A survey was conducted to estimate the VL incidence in villages around Tabarak Allah

Eliminating Human African Trypanosomiasis: Where Do We Stand and What Comes Next>

While the number of new detected cases of HAT is falling, say the authors, sleeping sickness could suffer the "punishment of success," receiving lower priority by public and private health institutions

Linking In Vitro and In Vivo Survival of Clinical Leishmania donovani Strains

BACKGROUND: Leishmania donovani is an intracellular protozoan parasite that causes a lethal systemic disease, visceral leishmaniasis (VL), and is transmitted between mammalian hosts by phlebotomine sandflies. Leishmania expertly survives in these 'hostile' environments with a unique redox system protecting against oxidative damage, and host manipulation skills suppressing oxidative outbursts of the mammalian host. Treating patients imposes an additional stress on the parasite and sodium stibogluconate (SSG) was used for over 70 years in the Indian subcontinent. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated whether the survival capacity of clinical L. donovani isolates varies significantly at different stages of their life cycle by comparing proliferation, oxidative stress tolerance and infection capacity of 3 Nepalese L. donovani strains in several in vitro and in vivo models. In general, the two strains that were resistant to SSG, a stress encountered in patients, attained stationary phase at a higher parasite density, contained a higher amount of metacyclic parasites and had a greater capacity to cause in vivo infection in mice compared to the SSG-sensitive strain. CONCLUSIONS/SIGNIFICANCE: The 2 SSG-resistant strains had superior survival skills as promastigotes and as amastigotes compared to the SSG-sensitive strain. These results could indicate that Leishmania parasites adapting successfully to antimonial drug pressure acquire an overall increased fitness, which stands in contrast to what is found for other organisms, where drug resistance is usually linked to a fitness cost. Further validation experiments are under way to verify this hypothesi

American Tegumentary Leishmaniasis: Is Antimonial Treatment Outcome Related to Parasite Drug Susceptibility?

BackgroundAntimonials are the first drug of choice for the treatment of American tegumentary leishmaniasis (ATL); however, their efficacy is not predictable, and this may be linked to parasite drug resistance. We aimed to characterize the in vitro antimony susceptibility of clinical isolates of Peruvian patients with ATL who were treated with sodium stibogluconate and to correlate this in vitro phenotype with different treatment outcomes MethodsThirty-seven clinical isolates were obtained from patients with known disease and treatment histories. These isolates were typed, and the susceptibility of intracellular amastigotes to pentavalent (SbV) and trivalent (SbIII) antimonials was determined ResultsWe observed 29 SbV-resistant isolates among 4 species of subgenus Viannia most of which exhibited primary resistance; isolates resistant only to SbIII; and 3 combinations of in vitro phenotypes: (1) parasites sensitive to both drugs, (2) parasites resistant to both drugs, and (3) parasites resistant to SbV only (the majority of isolates fell into this category). There was no correlation between in vitro susceptibility to both antimonials and the clinical outcome of therapy ConclusionAntimony insensitivity might occur in a stepwise fashion (first to SbV and then to SbIII). Our data question the definition of true parasite resistance to antimonials. Further studies of treatment efficacy should apply standardized protocols and definitions and should also consider host factor

Influence of Leishmania (Viannia) Species on the Response to Antimonial Treatment in Patients with American Tegumentary Leishmaniasis

Background. Pentavalent antimonials (SbV) are the first-line chemotherapy for American tegumentary leishmaniasis (ATL). There are, however, reports of the occurrence of treatment failure with these drugs. Few studies in Latin America have compared the response to SbV treatment in ATL caused by different Leishmania species. Methods. Clinical parameters and response to SbV chemotherapy were studied in 103 patients with cutaneous leishmaniasis (CL) in Peru. Leishmania isolates were collected before treatment and typed by multilocus polymerasechain-reaction restriction fragment—length polymorphism analysis. Results. The 103 isolates were identified as L. (Viannia) peruviana (47.6%), L. (V.) guyanensis (23.3%), L. (V.) braziliensis (22.3%), L. (V.) lainsoni (4.9%), L. (Leishmania) mexicana (1%), and a putative hybrid, L. (V.) braziliensis/L. (V.) peruviana (1%). L. (V.) guyanensis was most abundant in central Peru. Of patients infected with the 3 former species, 21 (21.9%) did not respond to SbV chemotherapy. The proportions of treatment failure (after 12 months of follow-up) were 30.4%, 24.5%, and 8.3% in patients infected with L. (V.) braziliensis, L. (V.) peruviana, and L. (V.) guyanensis, respectively. Infection with L. (V.) guyanensis was associated with significantly less treatment failure than L. (V.) braziliensis, as determined by multiple logistic regression analysis (odds ratio, 0.07 [95% confidence interval, 0.007-0.8]; P = .03). Conclusions. Leishmania species can influence SbV treatment outcome in patients with CL. Therefore, parasite identification is of utmost clinical importance, because it should lead to a species-oriented treatmen