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The Challenge of Parasite Control
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
As previously mentioned, for some diseases such as onchocerciasis and schistosomiasis current treatment relies almost entirely on a single drug. Even though resistance against ivermectin and praziquantel is not yet a major problem, the hints of emerging resistance described above underscore the need for new alternatives. The recent approval of moxidectin (see p. 447) is certainly encouraging as it provides health care professionals with a valuable, second option for onchocerciasis treatment. Like ivermectin, moxidectin, was originally developed for use in veterinary medicine. A derivative of a metabolic waste produced by soil bacteria in the genus Streptomyces, moxidectin works by selectively binding chloride-ion channels on neurons. Consequent disruption of neurotransmission results in paralysis and ultimately in death of the parasite.
Ivermectin and Moxidectin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
The antidiarrheal agent loperamide increased systemic bioavailability and delayed clearance of moxidectin (Lifschitz et al., 2002). Moxidectin is commonly combined with imidacloprid for additional protection against fleas in dogs and cats. The co-administration of the P-glycoprotein modulator quercetin enhanced moxidectin bioavailability (Dupuy et al., 2003), but conversely, verapamil was found to have no effect (Molento et al., 2004). Moxidectin was not found to cause alteration to CYP3A4 activity, and based on this, clinical metabolic drug–drug interactions with CYP3A4 substrates are unlikely to occur (Korth-Bradley et al., 2013).
The Challenge of Parasite Control
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2015
Eric S. Loker, Bruce V. Hofkin
As previously mentioned, for some diseases such as onchocerciasis and schistosomiasis current treatment relies on a single drug. Even though resistance against ivermectin and praziquantel is not yet a major problem, the hints of emerging resistance described above underscore the need for new alternatives. For onchocerciasis, clinical trials are currently under way for moxidectin, an anthelmintic currently used in veterinary medicine. A derivative of a metabolic waste produced by soil bacteria in the genus Streptomyces, moxidectin works by selectively binding chloride-ion channels on neurons. Consequent disruption of neurotransmission results in paralysis and ultimately in death of the parasite. For schistosomiasis, it has been suggested that a unique schistosome enzyme, thioredoxin glutathione reductase, might serve as a target for a new drug that could provide an alternative to praziquantel. The enzyme is crucial to the schistosome’s survival, as it allows the worm to evade reactive oxygen products generated by the host’s immune response. A new anti-schistosome drug that interfered with the enzyme would thus render schistosomes more vulnerable to immune destruction.
WHO Vision 2020: Have We Done It?
Published in Ophthalmic Epidemiology, 2023
Dalia Abdulhussein, Mina Abdul Hussein
Certain factors have limited the success of eradicating onchocerciasis. Firstly, although Ivermectin slows the spread of onchocerciasis, it does not eradicate the disease.26 WHO recommends treating onchocerciasis with ivermectin at least once yearly for 10–15 years.25 The parasite can survive for up to 15-years, therefore there needs to be a long-term treatment that can be sustained by the communities themselves as.26 One way in which this can be achieved is by using a milbemycin endectocide such as Moxidectin.26 Research has shown lower parasite transmission after treatment with Moxidectin compared to Ivermectin.27 This may be because Moxidectin can kill the adult worms responsible for the disease. Furthermore, there is incomplete mapping of all transmission zones and suboptimal program implementation.28
Moxidectin: an oral treatment for human onchocerciasis
Published in Expert Review of Anti-infective Therapy, 2020
Philip Milton, Jonathan I. D. Hamley, Martin Walker, María-Gloria Basáñez
Consequently, attention has focused on identifying alternative treatment strategies (ATS) aimed at accelerating progress toward elimination of transmission [13]. ATS include (not mutually exclusively) enhancing existing CDTI by increasing geographic and therapeutic coverage as well as treatment adherence; increasing treatment frequency (e.g. to biannual CDTI (bCDTI) or quarterly (3-monthly) treatment where necessary); deploying ground-based focal vector control (in contrast with the logistically demanding and large-scale aerial vector larviciding operations undertaken by the OCP); and using novel therapeutics [14]. Moxidectin represents a prime example of the latter, having been recently been approved by the US Food & Drug Administration (FDA) for the treatment of humans with onchocerciasis due to O. volvulus [15]. Hailing from the field of veterinary medicine, moxidectin is also a macrocyclic lactone and a potent microfilaricide, with a seemingly more prolonged microfilaricidal and/or embryostatic effect than ivermectin. Phase II and III clinical trials have demonstrated moxidectin’s superior clinical performance compared to ivermectin [16,17], indicating its potential to accelerate and enhance the feasibility of onchocerciasis elimination.
Current pharmacotherapeutic strategies for Strongyloidiasis and the complications in its treatment
Published in Expert Opinion on Pharmacotherapy, 2022
Dora Buonfrate, Paola Rodari, Beatrice Barda, Wendy Page, Lloyd Einsiedel, Matthew R. Watts
Moxidectin is a versatile, safe and stable molecule that is widely efficacious and used in veterinary medicine in different formulations. It comes in tablets, topical use or injectable for dogs, oral drench for sheep, and oral-gel for horses [76,83]. Its lipophilicity elicits and facilitates tissue deposition and a long duration of action. In dogs, moxidectin is usually administered once every 6/12 months in the prevention of the heartworm.