|
1000
|
Abstract/Summary
|
-
<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Background</jats:title>
<jats:p>In Europe, canine leishmaniasis is commonly caused by Leishmania infantum. Allopurinol is the main drug for long-term management of the disease, and clinical relapses of <jats:italic>L. infantum</jats:italic> infection treated with this drug are described. Resistance to allopurinol has been demonstrated in-vitro, but there is only little knowledge on in vivo resistance in dogs.</jats:p>
</jats:sec><jats:sec>
<jats:title>Findings</jats:title>
<jats:p>A two-year-old female spayed Akita Inu that was adopted from a breeding facility near Nice in France was initially diagnosed with primary immune-mediated hemolytic anemia. Immunosuppressive treatment was initiated, and the dog was referred for a second opinion to the Clinique Veterinaire Alliance in France. PCR testing for <jats:italic>L. infantum</jats:italic> was performed out of EDTA blood and IFA as well as ELISA testing out of serum. Resistance to allopurinol was associated with chromosome and gene copy number (CN) variations including a decrease in the S-adenosylmethionine synthetase (<jats:italic>METK</jats:italic>) gene CN.</jats:p>
</jats:sec><jats:sec>
<jats:title>Results</jats:title>
<jats:p>The dog showed pale mucous membranes, fever (39.1 °C), and a relapse of the anemia. The diagnosis of leishmaniasis was based on the cytological finding of <jats:italic>Leishmania</jats:italic> amastigotes (bone marrow, spleen, liver), positive PCR testing, and positive IFAT serology. The dog was treated with allopurinol over a period of 1316 days and additionally received two cycles of Glucantime® (meglumine antimoniate), before samples were submitted to the LABOKLIN laboratory to test for resistance against allopurinol. The laboratory work-up revealed mild thrombocytopenia, mild hyperproteinemia with hyperglobulinemia, a marked elevation of the c-reactive protein, and decreased iron concentration. Serum protein electrophoresis showed a polyclonal peak in the gamma globulins. Serology was positive in both ELISA (21.5 LE) and IFAT (1:1024). Quantitative PCR testing of blood was positive with low numbers of Leishmania (10/ml blood) at the timepoint of suspicion for resistance. The urinary protein-to-creatinine ratio was markedly elevated (2.5) and xanthine crystalluria was detected. A CN level of below 3 is considered suspicious for resistance, as revealed in the described Akita Inu dog.</jats:p>
</jats:sec><jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>Relapse of <jats:italic>L. infantum</jats:italic> infection after applying allopurinol for 1316 days due to resistance was suspected clinically. Positive PCR testing, consistent hematological and biochemistry abnormalities, and reduction in the <jats:italic>METK</jats:italic> gene CN backed up the clinical suspicion of resistance. Dogs infected with allopurinol resistant strains of <jats:italic>L. infantum</jats:italic> may represent a great risk for infection of naïve dogs, cats, and humans.
</jats:p>
</jats:sec><jats:sec>
<jats:title>Graphical Abstract</jats:title>
</jats:sec>
|
|
1000
|
Hinweis
|
-
DeepGreen-ID: 8a0ea806e6d44481ade63d635c246b65 ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
|
