Dataset Information

Efficacy of a low-dose praziquantel and fenbendazole protocol in the treatment of asymptomatic schistosomiasis in dogs.

ABSTRACT:

Background

Established treatment protocols for schistosomiasis (Heterobilharzia americana) in dogs are expensive. Anecdotal reports suggest that lower doses of praziquantel, combined with fenbendazole, may eliminate asymptomatic infections.

Objectives

Evaluate the efficacy of a low-dose praziquantel and fenbendazole protocol to manage asymptomatic schistosomiasis in dogs and compare fecal saline sedimentation (FSS) and fecal PCR (FPCR) for therapeutic monitoring.

Animals

Twelve asymptomatic dogs with positive FPCR and FSS results for schistosomiasis.

Methods

Prospective observational study. On day 0, dogs received praziquantel at a median dose of 5 mg/kg PO q8h for 2 days, with fenbendazole at 24 mg/kg PO q24h for 7 days. Fecal PCR and FSS were repeated in all dogs on days 30, 60, and 90.

Results

By day 30, 10 of 12 dogs were negative by FSS, but only 3 of 12 were negative by FPCR. By day 60, all 12 dogs were negative by FSS, and 8 of 12 had become negative by FPCR. By day 90, all 12 dogs remained negative by FSS, but 5 of 12 were positive by FPCR (including 2 that were negative by FPCR on day 60). Three dogs that were positive by FPCR on day 60 were re-treated and subsequently became both FPCR and FSS negative. One FPCR-positive dog developed a mild increase in serum ALP activity, another developed mild hypercalcemia, and a third developed diarrhea.

Conclusions and clinical importance

A low-dose praziquantel/fenbendazole protocol may be effective for asymptomatic schistosomiasis in some dogs, but monitoring to ensure treatment success is recommended. Fecal saline sedimentation and FPCR may demonstrate discrepant results, with FPCR being positive more frequently.

SUBMITTER: Cridge H

PROVIDER: S-EPMC8163111 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Human schistosomiasis is a neglected tropical disease caused by Schistosoma mansoni, S. haematobium, and S. japonicum. Praziquantel (PZQ) is the method of choice for treatment. Due to constant selection pressure, there is an urgent need for new therapies for schistosomiasis. Previous treatment of S. mansoni included the use of oxamniquine (OXA), a drug that is activated by a schistosome sulfotransferase (SULT). Guided by data from X-ray crystallography and Schistosoma killing assays more than 350 OXA derivatives were designed, synthesized, and tested. We were able to identify CIDD-0150610 and CIDD-0150303 as potent derivatives in vitro that kill (100%) of all three Schistosoma species at a final concentration of 71.5 μM. We evaluated the efficacy of the best OXA derivates in an in vivo model after treatment with a single dose of 100 mg/kg by oral gavage. The highest rate of worm burden reduction was achieved by CIDD -150303 (81.8%) against S. mansoni, CIDD-0149830 (80.2%) against S. haematobium and CIDD-066790 (86.7%) against S. japonicum. We have also evaluated the ability of the derivatives to kill immature stages since PZQ does not kill immature schistosomes. CIDD-0150303 demonstrated (100%) killing for all life stages at a final concentration of 143 μM in vitro and effective reduction in worm burden in vivo against S. mansoni. To understand how OXA derivatives fit in the SULT binding pocket, X-ray crystal structures of CIDD-0150303 and CIDD-0150610 demonstrate that the SULT active site will accommodate further modifications to our most active compounds as we fine tune them to increase favorable pharmacokinetic properties. Treatment with a single dose of 100 mg/kg by oral gavage with co-dose of PZQ + CIDD-0150303 reduced the worm burden of PZQ resistant parasites in an animal model by 90.8%. Therefore, we conclude that CIDD-0150303, CIDD-0149830 and CIDD-066790 are novel drugs that overcome some of PZQ limitations, and CIDD-0150303 can be used with PZQ in combination therapy.

Project description:BACKGROUND: Praziquantel has been used as first-line drug for chemotherapy of schistosomiasis since 1984. Besides praziquantel, artemether and artesunate have also been used for the control of this infectious disease since late 1990s. In this article, we conducted a systematic review and meta-analysis to evaluate the antischistosomal efficacy of different medication strategies including monotherapy or combination therapies of these drugs. RESULTS: A number of 52 trials from 38 articles published in peer-reviewed journals before July 2011 were selected for analysis after searching the following literature databases: the Cochrane Library, PubMed/Medline, ISI Web of Science, Chinese Biomedicine Literature Database, and China National Knowledge Infrastructure. Our meta-analyses showed that a dosage of 30-60 mg/kg praziquantel compared with placebo produced a protection rate of about 76% (95% CI: 67%-83%) for treating human schistosomiasis, which varied from 70% to 76% with no significant differences among the subspecies S. haematobium, S. japonicum or S. mansoni. Protection rates were higher when praziquantel doses were elevated, as concluded from the nRCTs results: the protection rate of praziquantel at 40 mg/kg was 52% (95% CI: 49%-55%), and it increased to 91% (95% CI: 88%-92%) when the dosages were elevated to 60/80/100 mg/kg divided two or more doses. Multiple doses of artemether or artesunate over 1- or 2-week intervals resulted in protection rates of 65% to 97% for preventing schistosomiasis, and increased doses and shorter medication intervals improved their efficacies. Praziquantel and artemisinin derivatives (artemether or artesunate) in combination resulted in a higher protection rate of 84% (95% CI: 64%-91%) than praziquantel monotherapy for treatment. praziquantel and artesunate in combination had a great protection rate of 96% (95% CI: 78%-99%) for preventing schistosomes infection. CONCLUSIONS: According to the results, praziquantel remains effective in schistosomiasis treatment, and multiple doses would improve its efficacy; meanwhile, praziquantel is also a good drug for preventing acute schistosomiasis morbidity. It's better to use multiple doses of artemether or artesunate with 1- or 2-week intervals for prevention against schistosome infection. Praziquantel and artemether or artesunate in combination perform better in treatment than praziquantel monotherapy, and they are especially suitable for treating the patients with repeated exposure to infected water.