Positive clinical experience with paromomycin sulfate in treatment of Balantioides coli (=Balantidium coli) natural infection in zoo-kept Mandrill monkeys (Mandrillus sphinx) and Western lowland gorillas (Gorilla gorilla gorilla).

Balantioides coli (=Balantidium coli), a large ciliated protozoan, is reported in multiple free-ranging and captive primate species, often in association with a clinical presentation that requires medical intervention. This report describes the clinical effectiveness of paromomycin sulfate against B.coli in zoo-kept mandrill monkeys (Mandrillus sphinx, at orally doses of 8-31 mg/kg, once daily (SID) for 7 days) and gorillas (Gorilla gorilla gorilla, at orally doses of 1.4-3.1 mg/kg, SID for 5 days).

Highly sensitive liquid chromatographic method combined with online ion suppression to remove interfering anions and mass spectrometry for impurity profiling of paromomycin sulfate.

A previously developed high-performance liquid chromatography method combined with pulsed amperometric detection allowed to separate many impurities of paromomycin. However, due to the presence of ion pairing agents and sodium hydroxide in the mobile phase, direct coupling to mass spectrometry for the identification of the chemical structures of the impurities was not an option. Indeed, ion suppression was encountered by trifluoroacetic acid and pentafluoroproponic acid in the mobile phase. A cation self-regenerating suppressor, which was originally designed for increasing analyte conductivity of ammonia and amines analysis in ion chromatography, was coupled between the liquid chromatography and ion trap-time of flight-mass spectrometry and almost all trifluoroacetic acid and pentafluoroproponic acid in the mobile phase was removed. The limit of detection of paromomycin in this integrated system improved significantly to 20 ng/ml (0.4 ng). The chemical structures of 19 impurities were elucidated and seven impurities were reported for the first time.

Efficacy of chitosan, a natural polysaccharide, against Cryptosporidium parvum in vitro and in vivo in neonatal mice.

Cryptosporidiosis is a zoonotic disease caused by species in the genus Cryptosporidium. In young ruminants, Cryptosporidium parvum causes economically significant disease with mild to severe clinical signs and occasional death. The typical clinical course in animals aged 1-3 weeks old is acute diarrhoea. Currently there are no available treatments that are fully effective against cryptosporidiosis in either humans or animals. Therefore there is a critical need for the development of new therapeutic agents. We adapted two in vitro culture systems (HCT-8 and Caco-2 cell lines) for C. parvum infection to investigate the "anticryptosporidial" activity of two chitosans; Chitosan NAG and Chitosan Mix. Chitosan-a naturally-occurring polysaccharide compound-has been found to be active against a variety of diseases, possessing both antimicrobial and anticancer properties. We investigated both chitosan's toxicity and effects on C. parvum in the two in vitro models. To evaluate chitosan's effects on oocyst shedding in vivo, CD-1 neonate mice were orally inoculated with C. parvum oocysts (Iowa strain), treated with chitosan, and compared to infected non-treated animals. Paromomycin, a classical drug used in veterinary medicine, was used as a reference compound. Immunofluorescence techniques were used to analyse the parasites. Our results showed significant reductions in Cryptosporidium oocyst viability (>95%) after oocyst pre-incubation with either paromomycin (P < 0.001), Chitosan Mix or Chitosan NAG (P < 0.001), for 24 h at 37 °C. Additionally, paromomycin, Chitosan Mix, and Chitosan NAG significantly inhibited C. parvum multiplication in HCT-8 and Caco-2 cell lines (P < 0.005). These effects were dose-dependent. In in vivo studies, treatment with both chitosans (Chitosan NAG, Chitosan Mix) or paromomycin sulfate significantly reduced parasite shedding in infected treated newborn mice (-56%, -34.5% and -58%, respectively). In conclusion, these findings provide the first in vitro and in vivo evidence of the anticryptosporidial activities of this natural polysaccharide.

Drug Targeting to Macrophages With Solid Lipid Nanoparticles Harboring Paromomycin: an In Vitro Evaluation Against L. major and L. tropica.

Leishmaniasis is a worldwide disease that leads to high mortality and morbidity in human populations. Today, leishmaniasis is managed via drug therapy. The drugs that are already in clinical use are limited to a number of toxic chemical compounds and their parasite drug resistance is increasing. It is therefore essential, in order to circumvent the current difficulties, to design a new anti-leishmanial drug treatment strategy. Besides producing new, active anti-leishmanial entities, another promising strategy could be developing novel delivery systems and formulations of the existing pharmaceutical ingredients to improve drug efficacy. In the present study, paromomycin sulfate (PM), as one of the promising anti-leishmanial drugs, was formulated in solid lipid nanoparticles (SLN), and its in vitro efficacy was investigated against different strains of Leishmania using a MTT test, Parasite-Rescue-Transformation-Assay, SYTO Green staining, and fluorescent microscope imaging. The results show that PM-loaded SLN is significantly more effective than PM in inhibiting parasite propagation (P < 0.05) and that cytotoxicity of PM-SLN formulations is size dependent. According to our results, delivery of the drugs to the macrophages via nanoparticle utilization seems to be an accessible and practical approach.

Paromomycin Sulfate Treatment in Histomoniasis Outbreaks in Three Commercial Turkey Flocks in the Fraser Valley of British Columbia, Canada.

Over the last couple of years, the number of histomoniasis cases in commercial turkeys has increased substantially in British Columbia, particularly in the Fraser Valley. Due to a lack of approved efficacious preventive or curative drugs in Canada, histomoniasis outbreaks have had significant economic and animal welfare impacts on the commercial turkey industry. In July 2020, Health Canada conditionally approved the treatment use of paromomycin sulfate on a case-by-case basis via an emergency drug release authorization. Three flocks infected with Histomonas meleagridis were treated with labeled-dose paromomycin sulfate in the feed shortly after presumptive diagnosis. Despite the treatment, two out of three flocks suffered significant losses. One flock suffered over 67% mortality by the eighth day of treatment. Due to significant production loss and animal welfare concerns, the flock was shipped early for mercy cull; thus sustained 100% production loss. Another flock experienced over 38% mortality by the end of the fourth week of treatment and was slaughtered early to minimize production loss. The treatment response in two out of three cases suggests that any curative effect of paromomycin is limited. Thus, future field evaluation should carefully consider the prophylactic use of paromomycin sulfate, especially on farms with recurrent outbreaks.

Paromomycin sulfate is an effective treatment for balantidiasis in captive cynomolgus monkeys.

There are few effective antimicrobial agents against Balantidium coli infection. The effect of paromomycin sulfate (PS) against B. coli was confirmed in this study of 596 captive cynomolgus monkeys. In several trials, the minimum dose and duration of oral administration of PS were 25 mg/day for 5 + 5 days, with a 2-day withdrawal interval. To facilitate daily PS administration, pumpkin cakes supplemented with PS were made, which not only resulted in precise effects but also increased the efficiency of preparation and administration of PS by the animal care staff. No cysts or trophozoites were detected at 14 or 16 days after the last treatments. There were no obvious differences in blood and biochemical parameters between before and after administration of PS. These results indicate that PS is effective for elimination of B. coli without hematological side effects. These data could contribute to the control of microbiological pathogens during veterinary care and colony management in primate facilities.

Effect of topical Nanoliposomes of Paromomycin on Rats Liver and Kidney.

BACKGROUND: Hepatotoxicity due to drugs is the most common cause of deaths. Nephrotoxicity of the drugs is usually associated with the drugs accumulation in renal tissue. Paromomycin sulfate (PMS) is an anti-leishmania drug. Although the topical approach for the treatment of leishmania is attractive, its use might cause nephrotoxicity and hepatotoxicity. OBJECTIVES: This study aimed to evaluate probable nephrotoxicity and hepatotoxicity of topically administered PMS liposomes. MATERIALS AND METHODS: Nine groups of male rats were used in this study; each group consisted of 6 rats that were evaluated in 3 time periods of 10, 20, and 30 days. Three groups were placed in each time period; a control group did not receive any medicine; a negative control group received liposome without paromomycin sulfate; and a positive control group received nanoliposomal formulations containing paromomycin sulfate. Pharmaceutical formulation (topical form) was used 2 times a day in a 12-hour interval. At the end of the period, hepatic enzymes (ALT, AST, and ALK), BUN levels, and serum creatinine were measured. RESULTS: The results showed that no significant change was occurred in the amount of the above factors compared with the control group with the negative control group in 3 time periods (P > 0.05). The histopathological results of the liver and kidney showed that there was no difference in the between the negative control and positive control groups and the control group in the 10- and 20-day periods, and they had a normal structure. However, after the 30-day time period a reversible cellular inflammation in the liver and mild kidney necrosis was seen in the positive control group versus the control and negative control groups. CONCLUSIONS: In general, it can be said that the application of nanoliposomal paromomycin sulfate formulations for topical treatment of the cutaneous leishmaniasis does not create serious side effects in the short term, but its long-term use leads to mild renal and liver side effects that requires more attention.