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Allopurinol Resistance in Leishmania infantum from Dogs with Disease Relapse.

ABSTRACT: BACKGROUND:Visceral leishmaniasis caused by the protozoan Leishmania infantum is a zoonotic, life threatening parasitic disease. Domestic dogs are the main peridomestic reservoir, and allopurinol is the most frequently used drug for the control of infection, alone or in combination with other drugs. Resistance of Leishmania strains from dogs to allopurinol has not been described before in clinical studies. METHODOLOGY/PRINCIPAL FINDINGS:Following our observation of clinical disease relapse in dogs under allopurinol treatment, we tested susceptibility to allopurinol of L. infantum isolated from groups of dogs pre-treatment, treated in remission, and with disease relapse during treatment. Promastigote isolates obtained from four treated relapsed dogs (TR group) showed an average half maximal inhibitory concentration (IC50) of 996 ?g/mL. A significantly lower IC50 (P = 0.01) was found for isolates from ten dogs before treatment (NT group, 200 ?g/mL), as well as for five isolates obtained from treated dogs in remission (TA group, 268 ?g/mL). Axenic amastigotes produced from isolates of the TR group also showed significantly higher (P = 0.002) IC50 compared to the NT group (1678 and 671 ?g/mL, respectively). The lower sensitivity of intracellular amastigotes from the TR group relative to those from the NT group (P = 0.002) was confirmed using an infected macrophage model (6.3% and 20% growth inhibition, respectively at 300 ?g/mL allopurinol). CONCLUSIONS:This is the first study to demonstrate allopurinol resistance in L. infantum and to associate it with disease relapse in the canine host. These findings are of concern as allopurinol is the main drug used for long term control of the disease in dogs, and resistant L. infantum strains may enhance uncontrolled transmission to humans and to other dogs.

SUBMITTER: Yasur-Landau D

PROVIDER: S-EPMC4711794 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Allopurinol Resistance in Leishmania infantum from Dogs with Disease Relapse.

Yasur-Landau Daniel D Jaffe Charles L CL David Lior L Baneth Gad G

PLoS neglected tropical diseases 20160106 1

<h4>Background</h4>Visceral leishmaniasis caused by the protozoan Leishmania infantum is a zoonotic, life threatening parasitic disease. Domestic dogs are the main peridomestic reservoir, and allopurinol is the most frequently used drug for the control of infection, alone or in combination with other drugs. Resistance of Leishmania strains from dogs to allopurinol has not been described before in clinical studies.<h4>Methodology/principal findings</h4>Following our observation of clinical diseas ...[more]

PMID: 26735519

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Project description:BackgroundThree species of Leishmania cause disease in humans in Israel and are endemic in the Middle East: Leishmania infantum, Leishmania tropica and Leishmania major. These species infect dogs and cats, but little is known about their prevalence in pet populations and their clinical manifestations. A study on dog and cat Leishmania infection was conducted in a focus of human L. tropica infection in central Israel with the aim of getting insight on leishmaniosis in pets in an area where human infection is highly prevalent.MethodsBlood, demographic and clinical data were collected from dogs and cats brought for veterinary care in a focus of human L. tropica infection during 2018-2020. kDNA PCR and internal transcribed spacer1 high-resolution melt analysis PCR (ITS1 HRM PCR) with DNA sequencing were performed for the detection of Leishmania and species determination.ResultsForty-three of 189 dogs (22.8%) and 44 of 152 cats (28.9%) were positive for Leishmania spp. infection by kDNA PCR. The ITS1 HRM PCR detected six dogs (3.3%) infected with L. infantum and one (0.5%) with L. tropica, whereas six cats (3.9%) were found infected by L. infantum and five (3.3%) by L. tropica. Four of the five L. tropica-positive cats suffered from weight loss, four had azotemia, two with mild and two with severe azotemia and progressive renal disease. Three cats had gingivostomatitis; three had skin lesions with abscess and ulcers in two and scales and hair loss in another cat, which was also FIV +. This is the first report of feline L. tropica infection in Israel. Clinical information on cats with this infection from previous studies elsewhere is scarce.ConclusionsA high rate of Leishmania spp. infection, mostly estimated as sub-clinical, was found in dogs and cats admitted for veterinary care in an L. tropica focus. Among the animals in which infection could be characterized to the species level, more dogs were infected with L. infantum than with L. tropica while 5 of 11 cats were infected with L. tropica and had signs of systemic and skin disease not described before in feline L. tropica infection.

Project description:BackgroundThe sand fly Nyssomyia neivai is one of the most abundant species in Southern Brazil. It is frequently found in areas that are foci of visceral leishmaniasis in the state of Santa Catarina, caused by Leishmania infantum. In this region, the main vector of L. infantum, Lutzomyia longipalpis, has not been detected. In the absence of L. longipalpis, this study aimed to identify the sand fly fauna and diagnose any potential Leishmania spp. infection in sand flies and in dogs in a region of Southern Brazil that experienced a recent canine visceral leishmaniasis outbreak.MethodsThis report includes a survey of the sand fly fauna at the Zoonosis Control Center of the Municipality of Tubarão (Santa Catarina, Brazil). Molecular tests were conducted to investigate Leishmania spp. natural infection in sand flies using polymerase chain reaction (PCR). In positive females, in addition to morphological identification, molecular analysis through DNA barcoding was performed to determine the sand fly species. Additionally, the dogs were tested for the presence of Leishmania spp. using a non-invasive technique for the collection of biological material, to be assessed by PCR.ResultsA total of 3419 sand flies, belonging to five genera, were collected. Nyssomyia neivai was the most abundant species (85.8%), followed by Migonemyia migonei (13.3%), Pintomyia fischeri (0.8%), Evandromyia edwardsi (< 0.1%), and species of the genus Brumptomyia. (0.1%). Out of the 509 non-engorged females analyzed by PCR, two (0.4%) carried L. infantum DNA. The naturally infected females were identified as Ny. neivai, in both morphological and molecular analysis. In addition, two out of 47 conjunctival swabs from dogs tested positive for L. infantum, yielding an infection rate of 4.2%.ConclusionsThese results confirm the presence of Ny. neivai naturally infected with L. infantum in an area where dogs were also infected by the parasite, suggesting its potential role as a vector in Southern Brazil.

Dataset Information

Allopurinol Resistance in Leishmania infantum from Dogs with Disease Relapse.

Publications

Allopurinol Resistance in Leishmania infantum from Dogs with Disease Relapse.

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