Prevalence of Trypanosoma evansi in horses (Equus caballus) and donkeys (Equus asinus) in El-Bayadh district, southwestern Algeria

NO ABSTRACT AVAILABLETrypanosoma evansi is a parasite that causes surra in a variety of wild and domestic animals and is mainly transmitted by biting flies in Africa, Asia and Latin-America. Horses infected by Trypanosoma evansi present a chronic weight loss, icterus, oedema, anemia, abortions and neurological troubles. Due to this parasite, cases of human trypanosomiosis have been reported in different countries by contacting with infected animals. In this study, 206 healthy equines (177 horses and 29 donkeys) from El-Bayadh district, located in southwest Algeria, were tested for the presence of parasites in blood using Giemsa-stained blood films and for the presence of antibodies against T. evansi using CATT /T. evansi. While none of the equines showed detectable parasites in the blood, the individual seroprevalence of T. evansi was found to be 46.6% (CI 95%, 40.7-54.4%). Out of 98 positives samples, 56.1% (55/98) were shown at level 1 (+), 27.5% (27/98) at level 2 (++) and 16.3% (16/98) at level 3 (+++). The results show that out of 177 tested horses, 80 were seropositive to T. evansi, 45.2% (CI 95%, 37.8-52.5%) and out of 29 tested donkeys, 18 were seropositive to T. evansi, 62.1% (CI 95%, 44.4-79.7%). A questionnaire for the owners, targeted to associate risk factors for surra in horses, showed that environmental factors that are favorable for Tabanids, such as water and vegetation, but also promiscuity with dromedaries were positively associated with the seroprevalence rate in the horses. El-Bayadh district is a highly endemic region for surra in Algeria

Development of a murine infection model with Leishmania killicki, responsible for cutaneous Leishmaniosis in Algeria : application in pharmacology

In Algeria, Leishmania infantum, Leishmania major, and Leishmania killicki (Leishmania tropica) are responsible for cutaneous leishmaniosis. We established a murine model of L. killicki infection to investigate its infective capacity, some immunophysiopathological aspects, and its suitability for pharmacological purposes. Following the injection of L. major or L. killicki metacyclic promastigotes in the ear dermis of BALB/c mice, the course of infection was followed. The infection with L. killicki caused slower lesion formation than with L. major. The presence of L. killicki or L. major DNA and parasites was detected in the ear dermis and in lymph nodes, spleen, and liver. Lesions induced by L. killicki were nonulcerative in their aspect, whereas those caused by L. major were highly ulcerative and necrotic, which matches well with the lesion phenotype reported in humans for L. killicki and L. major, respectively. The treatment of L. killicki lesions by injection of Glucantime (R) significantly reduced the lesion thickness and parasite burden. Ear dermal injection of BALB/c mice constitutes a model to study lesions physiopathology caused by L. killicki and presents interest for in vivo screening of new compounds against this pathogen, emerging in Algeria

Molecular mechanisms of drug resistance in natural Leishmania populations vary with genetic background

The evolution of drug-resistance in pathogens is a major global health threat. Elucidating the molecular basis of pathogen drug-resistance has been the focus of many studies but rarely is it known whether a drug-resistance mechanism identified is universal for the studied pathogen; it has seldom been clarified whether drug-resistance mechanisms vary with the pathogen's genotype. Nevertheless this is of critical importance in gaining an understanding of the complexity of this global threat and in underpinning epidemiological surveillance of pathogen drug resistance in the field. This study aimed to assess the molecular and phenotypic heterogeneity that emerges in natural parasite populations under drug treatment pressure. We studied lines of the protozoan parasite Leishmania (L.) donovani with differential susceptibility to antimonial drugs; the lines being derived from clinical isolates belonging to two distinct genetic populations that circulate in the leishmaniasis endemic region of Nepal. Parasite pathways known to be affected by antimonial drugs were characterised on five experimental levels in the lines of the two populations. Characterisation of DNA sequence, gene expression, protein expression and thiol levels revealed a number of molecular features that mark antimonial-resistant parasites in only one of the two populations studied. A final series of in vitro stress phenotyping experiments confirmed this heterogeneity amongst drug-resistant parasites from the two populations. These data provide evidence that the molecular changes associated with antimonial-resistance in natural Leishmania populations depend on the genetic background of the Leishmania population, which has resulted in a divergent set of resistance markers in the Leishmania populations. This heterogeneity of parasite adaptations provides severe challenges for the control of drug resistance in the field and the design of molecular surveillance tools for widespread applicability

Immunization against Leishmania major Infection Using LACK- and IL-12-Expressing Lactococcus lactis Induces Delay in Footpad Swelling

BACKGROUND: Leishmania is a mammalian parasite affecting over 12 million individuals worldwide. Current treatments are expensive, cause severe side effects, and emerging drug resistance has been reported. Vaccination is the most cost-effective means to control infectious disease but currently there is no vaccine available against Leishmaniasis. Lactococcus lactis is a non-pathogenic, non-colonizing Gram-positive lactic acid bacterium commonly used in the dairy industry. Recently, L. lactis was used to express biologically active molecules including vaccine antigens and cytokines. METHODOLOGY/PRINCIPAL FINDINGS: We report the generation of L. lactis strains expressing the protective Leishmania antigen, LACK, in the cytoplasm, secreted or anchored to the bacterial cell wall. L. lactis was also engineered to secrete biologically active single chain mouse IL-12. Subcutaneous immunization with live L. lactis expressing LACK anchored to the cell wall and L. lactis secreting IL-12 significantly delayed footpad swelling in Leishmania major infected BALB/c mice. The delay in footpad swelling correlated with a significant reduction of parasite burden in immunized animals compared to control groups. Immunization with these two L. lactis strains induced antigen-specific multifunctional T(H)1 CD4(+) and CD8(+) T cells and a systemic LACK-specific T(H)1 immune response. Further, protection in immunized animals correlated with a Leishmania-specific T(H)1 immune response post-challenge. L. lactis secreting mouse IL-12 was essential for directing immune responses to LACK towards a protective T(H)1 response. CONCLUSIONS/SIGNIFICANCE: This report demonstrates the use of L. lactis as a live vaccine against L. major infection in BALB/c mice. The strains generated in this study provide the basis for the development of an inexpensive and safe vaccine against the human parasite Leishmania

Leishmania antimony resistance : what we know what we can learn from the field

Leishmania is the causative agent of various forms of leishmaniasis, a significant cause of morbidity and mortality. The clinical manifestations of the disease range from self-healing cutaneous and mucocutaneous skin ulcers to a fatal visceral form named visceral leishmaniasis or kala-azar. In the absence of any effective vaccine, the only means to treat and control leishmaniasis is affordable medication. The treatment choice is essentially directed by economic considerations; therefore, for a large majority of countries, chemotherapy relies only on the use of cheaper antimonial compounds. The emergence of antimonial therapy failure in India linked to proven parasite resistance has stressed questions about selective factors as well as transmission risk of drug resistance. Unfortunately, in most parts of the world, the frequency of parasite antimony resistance linked to treatment failure is unknown because of a lack of information on Leishmania antimony susceptibility. This information is crucial for addressing the risk of selection and transmission of drug-resistant parasites, particularly in areas where antimony is the only chemotherapeutic alternative. However, the poor knowledge about factors that favor selection of resistant parasites, the multiplicity of the agents that can play a role in the in vivo antileishmanial activity of antimony, and the lack of a standard protocol to diagnose and survey parasite resistance all contribute to insufficient monitoring of antimony resistance. In this review, we discuss on the factors potentially involved in the selection of antimony resistance in the field and discuss on the methods available for its diagnosis

Leishmania antimony resistance/ susceptibility in Algerian foci

Algeria is one of the most endemic countries for cutaneous and visceral forms of eishmaniosis.Strikingly, with more than 21,000 annual cases of cutaneous leishmaniosis recorded in 2010, the disease has a major public health impact. For all forms of leishmaniosis, the fi rst line treatment relies on antimonial containing drug i.e.,Glucantime®, developed during the 1950’s. As early as 1986, antimonial treatment failure was reported during&nbsp; utaneous leishmaniosis treatment. Linked to this therapeutic failure, Leishmania strains displaying a low susceptibility towards antimonials were isolated. Nevertheless,in Algeria, antimonial formulations still remain the first line drug for all clinical forms of leishmaniosis. Therefore, an urgent need of knowledge on the baseline antimony susceptibility status of parasites strains in Algeria is required. These pieces of knowledge will shed light not only on the prevalence of antimony resistance in this area but also on underlying factors triggering this drug resistance in natural populations.Here, we performed a review of the literature on what is known about epidemiology, treatment failure,and antimony-resistance, in Algeria. We bring information on underlying mechanisms acting in antimony resistant parasites and discuss their potential to be used for diagnostic purpose. This analysis will help to set up protocols aiming at detecting antimony resistant strains in Algeria and to test the risk of transmission,two steps that are essential to define public health policy in Algeria.</p

In vitro susceptibility to antimonials and amphotericin B of Leishmania infantum strains isolated from dogs in a region lacking drug selection pressure

The aim of this study was to evaluate the susceptibility to anti-leishmanial agents of 24 strains isolated from dogs living in the urban area of Alger lacking drug selection pressure. Two different Leishmania infantum zymodemes, MON-1 and MON-281, were identified in these dogs. The in vitro susceptibility to the main forms of antimonial and amphotericin were assessed on promastigote and amastigote life stages in culture. The results obtained for both parasite life stages were concordant whatever the molecule tested. Moreover, our data showed that isolates belonging to the relatively rare zymodeme of L. infantum, MON-281, were less susceptible to antimony than MON-1, when at the same time there was no significant difference for amphotericin B