The filarial and the antibiotics: Single or combination therapy using antibiotics for filariasis

Fordjour, Fatima Amponsah; Kwarteng, Alexander

doi:10.3389/fcimb.2022.1044412

Cited by 3 publications

(2 citation statements)

References 81 publications

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“…Since Wolbachia are Gram-negative bacteria, specific antibiotics have been used to eliminate the bacteria from their filarial host, leading to the eventual killing of the adult worms. Clinical trials with doxycycline have shown dramatic depletion (more than 99%) of Wolbachia from filarial nematodes (6-week treatment, 200 mg/day) that resulted in significant reduction of microfilaridermia and killing of O. volvulus adult worms [ 39 ] through the activation of apoptosis [ 40 ]. Importantly, treatment with such antibiotics is beneficial when people are co-infected with L. loa , a human filarial parasite that does not harbor an endosymbiont [ 39 ] but one, which, in high numbers, causes severe adverse events when individuals are treated with the drug ivermectin [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Repurposed Drugs That Activate Autophagy in Filarial Worms Act as Effective Macrofilaricides

Voronin,

Tricoche,

Peguero

et al. 2024

Pharmaceutics

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Onchocerciasis and lymphatic filariasis are two neglected tropical diseases caused by filarial nematodes that utilize insect vectors for transmission to their human hosts. Current control strategies are based on annual or biannual mass drug administration (MDA) of the drugs Ivermectin or Ivermectin plus Albendazole, respectively. These drug regimens kill the first-stage larvae of filarial worms (i.e., microfilariae) and interrupt the transmission of infections. MDA programs for these microfilaricidal drugs must be given over the lifetime of the filarial adult worms, which can reach 15 years in the case of Onchocerca volvulus. This is problematic because of suboptimal responses to ivermectin in various endemic regions and inefficient reduction of transmission even after decades of MDA. There is an urgent need for the development of novel alternative treatments to support the 2030 elimination goals of onchocerciasis and lymphatic filariasis. One successful approach has been to target Wolbachia, obligatory endosymbiotic bacteria on which filarial worms are dependent for their survival and reproduction within the human host. A 4–6-week antibiotic therapy with doxycycline, for example, resulted in the loss of Wolbachia that subsequently led to extensive apoptosis of somatic cells, germline, embryos, and microfilariae, as well as inhibition of fourth-stage larval development. However, this long-course regimen has limited use in MDA programs. As an alternative approach to the use of bacteriostatic antibiotics, in this study, we focused on autophagy-inducing compounds, which we hypothesized could disturb various pathways involved in the interdependency between Wolbachia and filarial worms. We demonstrated that several such compounds, including Niclosamide, an FDA-approved drug, Niclosamide ethanolamine (NEN), and Rottlerin, a natural product derived from Kamala trees, significantly reduced the levels of Wolbachia in vitro. Moreover, when these compounds were used in vivo to treat Brugia pahangi-infected gerbils, Niclosamide and NEN significantly decreased adult worm survival, reduced the release of microfilariae, and decreased embryonic development depending on the regimen and dose used. All three drugs given orally significantly reduced Wolbachia loads and induced an increase in levels of lysosome-associated membrane protein in worms from treated animals, suggesting that Niclosamide, NEN, and Rottlerin were effective in causing drug-induced autophagy in these filarial worms. These repurposed drugs provide a new avenue for the clearance of adult worms in filarial infections.

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Section: Discussionmentioning

confidence: 99%

Repurposed Drugs That Activate Autophagy in Filarial Worms Act as Effective Macrofilaricides

Voronin,

Tricoche,

Peguero

et al. 2024

Pharmaceutics

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“…Wolbachia, an endosymbiotic bacterium of the order Rickettsiales, is present in arthropods. There is a symbiotic relationship between Wolbachia and filarial worms that is responsible for the filarial worms' development, embryogenesis, fertility and viability [13]. Tetracyclines (doxycycline and minocycline) are known to have an action against rickettsiae and therefore have been used against these novel targets.…”

Section: Discussionmentioning

confidence: 99%

An interesting case of pulmonary infiltrates with eosinophilia: out of sight out of mind

Panjwani,

Salman,

Nabar

2023

Breathe

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The search for better treatment strategies for mansonellosis: an expert perspective

Ferreira

Crainey²,

Gobbi

2023

Expert Opinion on Pharmacotherapy

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The filarial and the antibiotics: Single or combination therapy using antibiotics for filariasis

Cited by 3 publications

References 81 publications

Repurposed Drugs That Activate Autophagy in Filarial Worms Act as Effective Macrofilaricides

Repurposed Drugs That Activate Autophagy in Filarial Worms Act as Effective Macrofilaricides

An interesting case of pulmonary infiltrates with eosinophilia: out of sight out of mind

The search for better treatment strategies for mansonellosis: an expert perspective

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