Approches innovantes dans la prévention et le traitement de la leishmaniose canine à Leishmania infantum en Algérie.

Abstract

Leishmaniasis is among the world’s most neglected diseases. Dogs are the main reservoirs/ hosts of Leishmania infantum, causative agent of both canine and human visceral leishmaniosis. Canine leishmaniasis (CanL) represents a public health problem as one of the most prevalent zoonotic diseases worldwide. In addition, dogs are competent reservoirs/hosts of several protozoan pathogens transmitted by blood-feeding arthropods. Throughout their long history of domestication, they have served as a link for the exchange of parasites among livestock, wildlife, and humans and therefore remain an important source of emerging and re-emerging diseases. In Algeria, while CanL is well known to be endemic, no data are available on other vectorborne protozoans. First, we investigated the occurrence and diversity of trypanosomes, piroplasms and Hepatozoon spp. and update the epidemiological status of CanL in dogs from Kabylia, northern Algeria. A total of 227 dogs from three regions of Kabylia were enrolled, including 77 dogs with clinical signs. Dogs were clinically examined and were tested for L. infantum antibodies using a Rapid Immuno-Migration (RIM™) and a quantitative indirect Immunofluorescence Antibody Test (IFAT). PCR screening and sequencing were performed for vectorborne protozoa. Sixty two percent (141/227) of dogs presented at least one infection, whereas 26% (59/227) were co-infected. L. infantum antibodies were detected in 35.7% (81/227) of dogs including 88.7% (68/77) of sick dogs. Molecular investigation revealed prevalence of: 6.6% (15/227), 13.2% (30/227), 41% (93/227) for Trypanosoma spp., B. vogeli and H. canis, respectively. T. evansi (3.1%) and potential new subspecies of T. congolense had been identified. Dog’s clinical status correlates positively with L. infantum antibody titers and the presence of co-infections. Susceptibility to CanL varied according to the dog's aptitude and guard dogs were more infected (51%) (P-value = 0.001). B. vogeli infection was more frequent in juveniles than adults (32% versus 9%, Pvalue <0 .001) and in females than males (21% versus 10%, P-value = 0.02). To our knowledge, this is the first report on vector-borne protozoa infected dogs in Algeria. Current results are important not only for animal health, but also to avoid serious public health and livestock problems. Rigorous surveillance and control plans for these canine diseases are required in this area to contain them, or at least reduce their spread. In addition, current CanL therapeutics present various drawbacks. They are toxic, expensive or ineffective, thus, there is a need for more effective, safer, and cheaper drugs. Second, we evaluated and to compared the efficacy of oral administration of artesunate or meglumine antimoniate/ allopurinol in dogs with clinical leishmaniasis. Forty-two dogs with naturally occurring clinical leishmaniasis were included in this open-label, simple randomized positive control clinical field trial with 6 months of follow-up. Dogs received meglumine antimoniate 100 mg/kg/day and allopurinol 30 mg/kg/day for 28 days (control group, n = 26) or artesunate 25 mg/kg/day for 6 days (test group, n = 16). The dogs were evaluated for their clinical evolution, parasite load (by qPCR) and humoral response at different time points: 0, 30, 90, and 180 days after treatment. Data analyses showed a significant improvement in both groups in clinical scores, parasitemia and antibody titers after treatment. Compared to the control group, the artesunate group showed significantly lower clinical score (P-value = 0.0001), lower parasitemia (P-value = 0.0001) and antibody titers after 6 months of follow-up. Compared to baseline values, a rapid, significant reduction (P-value < 0.012) in antibody levels, 2.28- versus 3.04-fold for the control versus artesunate groups, respectively, was observed 30 days after treatment. Antibody levels continued to decrease further in the artesunate group, where 58% of cases became seronegative at the 6-month follow-up. All qPCR-positive dogs were negative after treatment with artesunate, while 14.3% remained positive with the appearance of two new cases in the control group. Artesunate was well tolerated, and no side effects were recorded. Treatment failures were similar in both groups with 27.27% (6/22), including 18.18% (4/22) mortality in the control group, versus 26.66% (4/15), including 13.33% (2/15) mortality in the artesunate group. This is the first report showing the potential of artesunate in the treatment of dogs with clinical leishmaniasis. Artesunate showed higher efficacy than the current first-line treatment for CanL without any adverse effects. It could be a good alternative chemotherapy for CanL, and may be considered for further studies in human leishmaniases. Further clinical trials are needed to confirm these findings, to determine if there are relapses after treatment and if dogs remain infective to sandflies, to define the ideal therapeutic dosage and duration of treatment with artesunate. We recommend the use of artesunate in the treatment of CanL, until the risk of Plasmodium spp. resistance to artesunate related to this use is assessed, in malaria-free regions such as Algeria or even the entire Mediterranean basin.