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Lymphatic filariasis and onchocerciasis are two major neglected tropical diseases that are responsible for causing severe disability in 50 million people worldwide, whilst veterinary filariasis (heartworm) is a potentially lethal parasitic infection of companion animals. There is an urgent need for safe, short-course curative (macrofilaricidal) drugs to eliminate these debilitating parasite infections. We investigated combination treatments of the novel anti-Wolbachia azaquinazoline small molecule, AWZ1066S, with benzimidazole drugs (albendazole or oxfendazole) in up to four different rodent filariasis infection models: Brugia malayi--CB.17 SCID mice, B. malayi--Mongolian gerbils, B. pahangi--Mongolian gerbils, and Litomosoides sigmodontis-- Mongolian gerbils. Combination treatments synergised to elicit threshold (>90%) Wolbachia depletion from female worms in 5 days of treatment, using 2-fold lower dose-exposures of AWZ1066S than monotherapy. Short-course lowered dose AWZ1066S-albendazole combination treatments also delivered partial adulticidal activities and/or long-lasting inhibition of embryogenesis, resulting in complete transmission blockade in B. pahangi and L. sigmodontis gerbil models. We determined that short-course AWZ1066S-albendazole co-treatment significantly augmented the depletion of Wolbachia populations within both germline and hypodermal tissues of B. malayi female worms and in hypodermal tissues in male worms, indicating that anti-Wolbachia synergy is not limited to targeting female embryonic tissues. Our data provides pre-clinical proof-of-concept that sub-seven-day combinations of rapid-acting novel anti-Wolbachia agents with benzimidazole anthelmintics are a promising curative and transmission-blocking drug treatment strategy for filarial diseases ofmedical and veterinary importance. [ABSTRACT FROM AUTHOR]

This paper studies wave localization in chains of finitely many resonators. There is an extensive theory predicting the existence of localized modes induced by defects in infinitely periodic systems. This work extends these principles to finite‐sized systems. We consider one‐dimensional, finite systems of subwavelength resonators arranged in dimers that have a geometric defect in the structure. This is a classical wave analog of the Su–Schrieffer–Heeger model. We prove the existence of a spectral gap for defectless finite dimer structures and find a direct relationship between eigenvalues being within the spectral gap and the localization of their associated eigenmode. Then, for sufficiently large‐size systems, we show the existence and uniqueness of an eigenvalue in the gap in the defect structure, proving the existence of a unique localized interface mode. To the best of our knowledge, our method, based on Chebyshev polynomials, is the first to characterize quantitatively the localized interface modes in systems of finitely many resonators. [ABSTRACT FROM AUTHOR]