Prior to treatment, assessment of renal and liver function is recommended so that dogs more susceptible to drug toxicity can be identified. Close monitoring of such animals is required during therapy. Initial treatment with allopurinol alone may be advisable in some cases with severe renal dysfunction, although this alone may be inadequate to treat active leishmaniosis.
The most commonly used protocols for treatment of canine leishmaniosis in Europe are:
- combination of meglumine antimonate (75-100 mg/kg SC every 24 hours for 4 weeks) and allopurinol 20 mg/kg PO daily (can be in divided doses) for 1 month followed by allopurinol alone for at least 6-12 months.
- combination of miltefosine (2 mg/kg PO every 24 hours for 4 weeks) and allopurinol 20 mg/kg PO daily (can be in divided doses) for 1 month followed by allopurinol alone for at least 6-12 months.
Meglumine antimonate and miltefosine are licensed for the treatment of canine leishmaniosis in several European countries but require importation and authorisation in non-endemic countries (see below).
Allopurinol alone may be considered in asymptomatic dogs with marginal serology and that are PCR negative or positive on PCR but with only low levels of Leishmania, particularly if they are resident in non-endemic countries.
Other therapeutic protocols less favoured include amphoteracin B, metronidazole in combination with spiramycin, marbofloxacin.
Side effects of treatment
Meglumine antimonate: pain on injection, injection site cellulitis/abscesses, potential nephrotoxicity, problematic due to need for daily injections
Miltefosine: vomiting and diarrhoea, potential renal toxicity
Allopurinol: xanthine urolithiasis especially if long treatment required (> 12 months) – can monitor via ultrasound of bladder and kidneys
Summary treatment of leishmaniosis
| Drug | Treatment protocol | Notes/ side-effects | |
|---|---|---|---|
| Protocol A | **Meglumine antimonate (e.g. Glucantime) in combination with *Allopurinol |
100 mg/kg SC q24h for 28 days plus 10-15 mg/kg PO q12-24h hrs for 6-12 months |
Pain, swelling at injection site, renal dysfunction, increase in liver enzymes
Xanthine urolithiasis |
| Protocol B | **Miltefosine (e.g. Milteforan) in combination with *Allopurinol |
2mg/kg PO q24h for 28 days plus 10-15 mg/kg PO q12-24h hrs for 6-12 months |
Vomiting, diarrhoea, potential renal toxicity Xanthine urolithiasis |
*Drugs are not licensed for this purpose in the UK
** Drugs require importation, SIC
Authorisation and importing Glucantime and Miltefosine in the UK
Veterinary surgeons wishing to import these drugs need to apply to the Veterinary Medicines Directorate (VMD) for a Special Import Certificate (SIC). The application requires information about the veterinary surgeon, the animal, the product and the amount required. The country of origin of the drug being imported is also required; meglumine antimonate can be imported from France and Spain, and miltefosine from Spain. An online web-based service for SICs is available for veterinary surgeons at the VMD’s Special Import site: http://www.vmd.gov.uk/sis/default.aspx.
Go to http://www.vmd.gov.uk and click on On-Line Services and select Special Import Site
- Select: Special Import Certificate (Europe medicinal product) option, which will then require you to enter your RVS membership number to continue.
- This on-line application is now free
If a veterinary surgeon has never applied for a SIC before, then before this can be done online the vet has to either succesfully obtain a postal application (forms are on the website) or have given their name, RCVS number, practice name and address to a member of the VMD Licensing Administration team (easily done by telephoning 01932 338442 and giving details). Following this the vet can use the online facility to apply for any SIC, irrespective of the drug imported. All of the vet’s details will be stored. This is a quick and convenient process. When completed and accepted as valid on the web-site, the certificate can be printed out and used.
In addition to applying for an SIC, the veterinary surgeon will need to either:
- identify a UK-based importing drug wholesaler to import the drug on their behalf from another EU country
OR - arrange to import it themselves direct from a wholesale drug supplier in an EU country where the product is licensed.
If using a UK-based importing drug wholesaler, they will require copy of a valid SIC as part of the ordering process. If the drug is being imported direct by the veterinary surgeon from an EU wholesale drug supplier, the SIC may also be required or at least confirmation that the importer is a registered veterinary surgeon.
NB. Virbac UK now have a limited holding stock of Miltefosine here in the UK. Please contact them but you must have a current SIC as well.
Monitoring and response to therapy
Clinical response to combination therapy varies between good to poor depending on the degree of organ dysfunction. The majority of dogs improve clinically during the first month of treatment. Dogs with renal dysfunction have a poorer response. Improvements in urine protein: creatinine ratio, globulin levels and qPCR results are also seen but may take longer to return to the reference ranges. Antibody titres remain elevated for longer periods of time and are not useful for monitoring treatment until at least 6 months after starting.
Monitoring of dogs is recommended at the following approximate time points after starting treatment: 1 month, then every 3-4 months for a year then 6-12 monthly thereafter if required.
Monitoring at 1 and 4 month checks should include evaluation of any organ dysfunction, serum albumin and globulin levels, urine protein: creatinine ratio and blood qPCR. In successful treatment, these will often normalise during this period. For the 6 month -12month checks, antibody titres should be added too.
After one year of successful treatment, consideration may be given to discontinuing allopurinol, particularly in a non-endemic region. All clinicopathological parameters should be within reference range and the antibody titres borderline or negative before treatment is stopped. If a bone marrow sample is available at this time, a negative qPCR provides further support for discontinuation. Discontinuation of therapy is ultimately dependent on recovery of the dog’s immunological ability to control the infection. Some dogs never regain this ability and will require continual therapy to keep the infection under control
Prognosis
Although clinical response is good in the majority of dogs, it is guarded to poor in dogs with evidence of disseminated immune-mediated disease, and those with severe renal disease or failure.
Parasitological cure is considered rare although many dogs with low infection loads may remain asymptomatic for long periods.