Anti-Wolbachia therapy for onchocerciasis & lymphatic filariasis

Abstract

Onchocerciasis and lymphatic filariasis (LF) are human filarial diseases belonging to the group of neglected tropical diseases, leading to permanent and long-term disability in infected individuals in the endemic countries such as Africa and India. Microfilaricidal drugs such as ivermectin and albendazole have been used as the standard therapy in filariasis, although their efficacy in eliminating the diseases is not fully established. Anti-Wolbachia therapy employs antibiotics and is a promising approach showing potent macrofilaricidal activity and also prevents embryogenesis. This has translated to clinical benefits resulting in successful eradication of microfilarial burden, thus averting the risk of adverse events from target species as well as those due to co-infection with loiasis. Doxycycline shows potential as an anti-Wolbachia treatment, leading to the death of adult parasitic worms. It is readily available, cheap and safe to use in adult non-pregnant patients. Besides doxycycline, several other potential antibiotics are also being investigated for the treatment of LF and onchocerciasis. This review aims to discuss and summarise recent developments in the use of anti-Wolbachia drugs to treat onchocerciasis and LF.

Wolbachia: endosymbiont of onchocercid nematodes and their vectors

“…Despite doxycycline being adopted to treat filarial diseases, potential difficulties (e.g. drug adherence, toxicity, resistance, financial cost, contraindications in pregnant women and children) limit its use in the public health MDA programmes [ 127 ]. Promising in vitro drug trials with new antibiotics (e.g.…”

“…Promising in vitro drug trials with new antibiotics (e.g. berberine, rapamycin, globomycin, succinyl acetone) [ 106 , 154 – 156 ] and the effectiveness of non-antimicrobial compounds such as anti-oxidants and anti-histamines open a new window onto filarial treatment [ 127 ]. Further clinical trials using these drugs may provide an innovative strategy for anti- Wolbachia treatment, eventually reducing the duration of treatment.…”

“…In addition, it is suggested that together with filarial antigens, Wolbachia may induce generation of NO, which aids in the peripheral tolerance through apoptosis of antigen-specific T lymphocytes [ 125 ]. This manipulation of the host immune system helps to increase the longevity of onchocercid nematodes [ 126 , 127 ] (Fig. 2 ).…”

“…Meta-analytical modelling suggests that a 4-week doxycycline course suffices to eliminate Wolbachia with low chances of developing drug resistance when compared to other antibiotics like penicillin or fluoroquinolones [ 133 , 134 ]. However, the limited use of this drug in pregnancy, lactating mothers and children motivated the scientific community to search for other anti- Wolbachia drugs [ 127 , 131 ]. As a result, more than 2 million compounds have been tested in insect cell lines and A∙WOL was formed with the objective to identify new anti- Wolbachia drugs with a short course of therapy, which could be safe in contraindicated groups [ 135 , 136 ].…”

New Molecular Data on Filaria and its Wolbachia from Red Howler Monkeys (Alouatta macconnelli) in French Guiana—A Preliminary Study

“…The parasites’ endosymbiotic Wolbachia are implicated in severe inflammatory-mediated filarial diseases [ 13 , 14 , 15 , 16 ]. Anti-wolbachial therapies, based on the administration of antibiotics, are known to be effective against the most common filariasis caused by Brugia spp., i.e., W. bancrofti, Mansonella perstans and D. immitis [ 17 , 18 , 19 ]. The Wolbachia -filaria relationship is species-specific, wherein each filariid has a specific genotype of Wolbachia [ 11 ], thus providing an additional target suitable for the diagnosis of filarial infections [ 20 ], especially when occurring in dead-end hosts, as is the case in D. immitis in human and cats [ 21 , 22 ].…”