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.
BackgroundPeste des petits ruminants (PPR) is a contagious disease listed by the World Organisation for Animal health (OIE) as being a specific hazard. It affects sheep, goats, and wild ungulates, and is prevalent throughout the developing world particularly Asia, the Middle East, and Africa. PPR has been targeted for eradication by 2030 by the Food and Agriculture Organization of the United Nations (FAO) and the OIE, after the successful eradication of the related disease, rinderpest in cattle. PPR was first reported in 1942 in the Ivory Coast in Western Africa and has since extended its range in Asia, the Middle East, and Africa posing an immediate threat of incursion into Europe, South East Asia and South Africa. Although robust vaccines are available, the use of these vaccines in a systematic and rational manner is not widespread, resulting in this devastating disease becoming an important neglected tropical disease in the developing world.MethodologyWe isolated and characterized the PPR virus from an outbreak in Cheraga, northern Algeria, during October 2015 by analyzing the partial N-gene sequence in comparison with other viruses from the Maghreb region. As well as sequencing the full length viral genome and performing real-time RT-PCR on clinical samples. Maximum-likelihood and Bayesian temporal and phylogeographic analyses were performed to assess the persistence and spread of PPRV circulation from Eastern Africa in the Maghreb region of North Africa.ConclusionsRecent PPR outbreaks in Cheraga, in the northern part of Algiers (October 2015) and North-West Morocco (June, 2015) highlight that PPRV has spread to the northern border of North Africa and may pose a threat of introduction to Europe. Phylogeographic analysis suggests that lineage IV PPRV has spread from Eastern Africa, most likely from the Sudan 2000 outbreak, into Northern Africa resulting in the 2008 Moroccan outbreak. Maximum-likelihood and Bayesian analysis shows that these North African viruses cluster closely together suggesting the existence of continual regional circulation. Considering the same virus is circulating in Algeria, Morocco and Tunisia, implementation of a common Maghreb PPR eradication strategy would be beneficial for the region.
Query (Q) fever is a globally distributed zoonotic disease caused by Coxiella burnetii, a bacterial agent for which ruminants are the most prevalent natural reservoir. Data regarding Q fever infection in camels in Algeria are limited. Therefore, a survey to detect seroprevalence of C. burnetii antibodies was conducted among healthy camel populations in a vast area in southeastern Algeria to determine distribution of the Q fever causative organism and to identify risk factors associated with infection. Between January and March 2016, blood samples were collected from 184 camels and serum samples were subsequently analysed using a commercial Enzyme-Linked Immunosorbent Assay (ELISA) kit. At the time of blood collection, a questionnaire investigating 13 potential predisposing factors associated with C. burnetii seropositivity was completed for every dromedary camel and herd. Results were analysed by a chi-square (χ2) test and multivariate logistic regression. The seroprevalence of C. burnetii at the animal level was 71.2% (95% CI: 65.2–78.3) and 85.3% (95% CI: 72.8–97.8) at the herd level. At the animal level, differences in seroprevalence were observed because of herd size, animal age, animal sex, presence of ticks and contact with other herds. A multivariable logistic regression model identified three main risk factors associated with individual seropositivity: (1) age class > 11 years (OR = 8.81, 95% CI: 2.55–30.41), (2) herd size > 50 head (OR = 4.46, 95% CI: 1.01–19.59) and (3) infestation with ticks (OR 2.2; 95% CI: 1.1–4.5). This study of seroprevalence of C. burnetii infection in camels in Algeria revealed a high seroprevalence of Q fever in camel populations in southeastern Algeria and provided strong evidence that Q fever represents an economic, public health and veterinary concern. Appropriate measures should be taken to prevent the spread of C. burnetii and to reduce the risk of Q fever in farm animals and humans in this agro-ecologically and strategically important region of North Africa.
BackgroundIn Algeria, the treatment of visceral and cutaneous leishmanioses (VL and CL) has been and continues to be based on antimony-containing drugs. It is suspected that high drug selective pressure might favor the emergence of chemoresistant parasites. Although treatment failure is frequently reported during antimonial therapy of both CL and VL, antimonial resistance has never been thoroughly investigated in Algeria. Determining the level of antimonial susceptibility, amongst Leishmania transmitted in Algeria, is of great importance for the development of public health policies.Methodology/Principal findingsWithin the framework of the knowledge about the epidemiology of VL and CL amassed during the last 30 years, we sampled Leishmania isolates to determine their susceptibility to antimony. We analyzed a total of 106 isolates including 88 isolates collected between 1976 and 2013 in Algeria from humans, dogs, rodents, and phlebotomines and 18 collected from dogs in France. All the Algerian isolates were collected in 14 localities where leishmaniasis is endemic. The 50% inhibitory concentrations (IC50) of potassium antimony tartrate (the trivalent form of antimony, Sb(III)) and sodium stibogluconate (the pentavalent form of antimony, Sb(V)) were determined in promastigotes and intramacrophage amastigotes, respectively. The epidemiological cutoff (ECOFF) that allowed us to differentiate between Leishmania species causing cutaneous or visceral leishmaniases that were susceptible (S+) or insusceptible (S-) to the trivalent form of antimony was determined. The computed IC50 cutoff values were 23.83 μg/mL and 15.91 μg/mL for VL and CL, respectively. We report a trend of increasing antimony susceptibility in VL isolates during the 30-year period. In contrast, an increase in the frequency of S- phenotypes in isolates causing CL was observed during the same period. In our study, the emergence of S- phenotypes correlates with the inclusion of L. killicki (syn: L. tropica) isolates that cause cutaneous leishmaniasis and that have emerged in Algeria during the last decade.Conclusion/SignificanceOur results provide insight into the spatiotemporal dynamics of Leishmania antimony susceptibility in Algeria. We highlight the need for the future implementation of an effective methodology to determine the antimony susceptibility status of Leishmania isolates to detect the emergence of and prevent the dissemination of drug-resistant strains.
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