In vitro efficacy of anthelmintics on Angiostrongylus cantonensis L3 larvae

Abstract

Angiostrongylus cantonensis is the leading cause of eosinophilic meningitis worldwide, with life-threatening complications if not managed correctly. Previous in vitro studies have utilized change in motility patterns of adult female worms to assess the efficacy of anthelmintics qualitatively. However, it is the third stage larvae (L3) that are infectious to humans. With differential staining using propidium iodide penetration as the indicator of death, we can distinguish between dead and live larvae. This assay has enabled us to quantify the in vitro efficacy of nine clinically established anthelmintics on A. cantonensis L3. All drugs were tested at a 1 mm concentration. Piperazine and niclosamide were ineffective in inducing larval death; however, albendazole sulfoxide, pyrantel pamoate, diethylcarbamazine, levamisole and praziquantel were effective as compared to unexposed controls (P < 0.05). Ivermectin and moxidectin did not induce significant levels of mortality, but they considerably reduced larval motility almost immediately. This study indicates the need for further in vivo studies to determine the optimal dose and time frame for post-infection treatment with anthelmintics that demonstrated efficacy.

Susceptibility of Angiostrongylus cantonensis Larvae to Anthelmintic Drugs

“…These drugs are the major course of treatment against parasitic nematode infections. The only previous systematic investigation in vitro of anthelmintic drugs on A. cantonensis has been described recently using third-stage larvae ( Jacob et al, 2021 ). However, drugs were tested at a very high concentration (1 mM).…”

“…However, these studies were done using adult worms. The only previous studies in vitro of anthelmintic agents on A. cantonensis has been described recently against third-stage larvae (L3) at a very high drug concentration ( Jacob et al, 2021 ) but the activity on first-stage larvae (L1) was not assessed. Using the L1 larvae isolated from feces of an A. cantonensis -infected rat, which allows markedly higher throughput than the third-stage larvae and adult worm-based assay, the purpose of this study was to evaluate the antiparasitic activity of the major anthelmintic drugs, including those listed in the WHO Model List of Essential Medicines.…”

Clinical Efficacy and Safety of Albendazole and Other Benzimidazole Anthelmintics for Rat Lungworm Disease (Neuroangiostrongyliasis): A Systematic Analysis of Clinical Reports and Animal Studies

“…Benzimidazoles are one of the few classes of anthelmintics that are effective against A. cantonensis [ 157 ], especially albendazole, which is currently the only available FDA-approved benzimidazole known to be capable of crossing the BBB [ 11 ]. An increasing number of guidelines recommend the use of albendazole–corticosteroid cotherapy for the management of neuroangiostrongyliasis, for example, the Sydney Children’s Hospital Network, Australia (2018) [ 158 ]; the Children’s Health Queensland Hospital and Health Services, Australia (2019) [ 159 ]; the Hilo Medical Center, Hawaii (2020) [ 160 ]; and the Hawaii Governor’s Joint Task Force on Rat Lungworm Disease Clinical Subcommittee [ 9 ].…”

“…An increasing number of guidelines recommend the use of albendazole–corticosteroid cotherapy for the management of neuroangiostrongyliasis, for example, the Sydney Children’s Hospital Network, Australia (2018) [ 158 ]; the Children’s Health Queensland Hospital and Health Services, Australia (2019) [ 159 ]; the Hilo Medical Center, Hawaii (2020) [ 160 ]; and the Hawaii Governor’s Joint Task Force on Rat Lungworm Disease Clinical Subcommittee [ 9 ]. Experimental studies have also demonstrated the in vitro efficacy of albendazole on A. cantonensis L3 [ 157 , 161 ]. However, doubt remains regarding albendazole’s safety, primarily due to concerns that it may cause further inflammation and associated complications induced by the killed larvae in the brain [ 3 , 10 ].…”

Angiostrongylus cantonensis and neuroangiostrongyliasis (rat lungworm disease): 2020

“…The latest research on infection in non-human species is described (Feckova et al, 2021;Malik et al, 2021;Tsai and Chen, 2021;Wun et al, 2021a, b). Methods for preventing infection or reducing risks of human exposure (Howe et al, 2021;Steel et al, 2021), documentation of chronic sequelae (Meyer, 2021) and updates on research in disease diagnosis and treatment (Ansdell et al, 2021;Eamsobhana et al, 2021;Jacob et al, 2021;Jarvi et al, 2021) are provided. We hope these research papers will provide clinicians, researchers, educators and the general public with information that might help to reduce the risk of infection in humans and other animals, develop more efficient and targeted diagnostic methods, rationalise therapeutic approaches in acute and chronic cases, and direct future research on this fascinating but potentially destructive disease.…”