The Efficacy of Doxycycline Treatment on Mansonella perstans Infection: An Open-Label, Randomized Trial in Ghana

Debrah, Linda Batsa; Phillips, Richard Odame; Pfarr, Kenneth; Klarmann‐Schulz, Ute; Opoku, Vera Serwaa; Nausch, Norman; Owusu, Wellington; Mubarik, Yusif; Sander, Anna-Lena; Lämmer, Christine; Ritter, Manuel; Layland, Laura E.; Jacobsen, Marc; Debrah, Alexander Yaw; Hoerauf, Achim

doi:10.4269/ajtmh.18-0491

Cited by 35 publications

(27 citation statements)

References 39 publications

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“…Depletion of Wolbachia endosymbionts from filariae by doxycycline therapy was previously shown to inhibit filarial development and to mediate the clearance of MF and permanent inhibition of filarial embryogenesis in patients with onchocerciasis, lymphatic filariasis or mansonelliasis [22,[42][43][44][45][46][47], leading to a slow and well-tolerated killing of the adult filariae after 18 months in lymphatic filariasis [48,49] (ISRCTN15216778), and later in onchocerciasis [50,51]. However, while making it the first safe macrofilaricidal drug for onchocerciasis, the long 4-5-week treatment regimen with doxycycline and its contraindications limit its broader use beyond individual prescriptions.…”

Section: Discussionmentioning

confidence: 99%

Corallopyronin A for short-course anti-wolbachial, macrofilaricidal treatment of filarial infections

et al. 2020

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Current efforts to eliminate the neglected tropical diseases onchocerciasis and lymphatic filariasis, caused by the filarial nematodes Onchocerca volvulus and Wuchereria bancrofti or Brugia spp., respectively, are hampered by lack of a short-course macrofilaricidal–adult-worm killing–treatment. Anti-wolbachial antibiotics, e.g. doxycycline, target the essential Wolbachia endosymbionts of filariae and are a safe prototype adult-worm-sterilizing and macrofilaricidal regimen, in contrast to standard treatments with ivermectin or diethylcarbamazine, which mainly target the microfilariae. However, treatment regimens of 4–5 weeks necessary for doxycycline and contraindications limit its use. Therefore, we tested the preclinical anti-Wolbachia drug candidate Corallopyronin A (CorA) for in vivo efficacy during initial and chronic filarial infections in the Litomosoides sigmodontis rodent model. CorA treatment for 14 days beginning immediately after infection cleared >90% of Wolbachia endosymbionts from filariae and prevented development into adult worms. CorA treatment of patently infected microfilaremic gerbils for 14 days with 30 mg/kg twice a day (BID) achieved a sustained reduction of >99% of Wolbachia endosymbionts from adult filariae and microfilariae, followed by complete inhibition of filarial embryogenesis resulting in clearance of microfilariae. Combined treatment of CorA and albendazole, a drug currently co-administered during mass drug administrations and previously shown to enhance efficacy of anti-Wolbachia drugs, achieved microfilarial clearance after 7 days of treatment at a lower BID dose of 10 mg/kg CorA, a Human Equivalent Dose of 1.4 mg/kg. Importantly, this combination led to a significant reduction in the adult worm burden, which has not yet been published with other anti-Wolbachia candidates tested in this model. In summary, CorA is a preclinical candidate for filariasis, which significantly reduces treatment times required to achieve sustained Wolbachia depletion, clearance of microfilariae, and inhibition of embryogenesis. In combination with albendazole, CorA is robustly macrofilaricidal after 7 days of treatment and fulfills the Target Product Profile for a macrofilaricidal drug.

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Section: Discussionmentioning

confidence: 99%

Corallopyronin A for short-course anti-wolbachial, macrofilaricidal treatment of filarial infections

et al. 2020

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“…For loiasis the treatment of choice is DEC [30] or IVM + ALB [31] in case of DEC unavailability. Instead, for M. perstans infection the treatment of choice seems to be doxycycline [32,33], although the treatment usually preferred in European countries is still mebendazole.…”

Section: Discussionmentioning

confidence: 99%

Performance of two serodiagnostic tests for loiasis in a Non-Endemic area

et al. 2020

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Loiasis, caused by the filarial nematode Loa loa, is endemic in Central and West Africa where about 10 million people are infected. There is a scarcity of convenient, commercial diagnostics for L. loa. Microscopy requires trained personnel and has low sensitivity, while the serodiagnosis is currently not standardized. Individual case management is also important in non-endemic countries to treat migrants, expatriates and tourists. We retrospectively compared the performance of a Loa Antibody Rapid Test (RDT) and a commercial ELISA pan-filarial test on 170 patients, 65 with loiasis [8 with eyeworm, 29 with positive microfilaremia, 28 with neither microfilaremia nor history of eyeworm but eosinophilia and history of Calabar swelling (probable loiasis)], 95 with other common parasitic infections and no previous exposure to L. loa (37 with M. perstans, 1 with Brugia sp., 18 with strongyloidiasis, 20 with schistosomiasis, 5 with hookworm, 4 with Ascaris lumbricoides infection, 10 with hyperreactive malarial splenomegaly), and 10 uninfected controls. The sensitivity of the RDT and of the ELISA were 93.8% (61/65) and 90.8% (59/65), respectively. For the RDT, most of the cross-reactions were observed in patients with M. perstans: 7/37 (18.9%), followed by 1/10 (10%) with hyper-reactive malarial splenomegaly and 1/20 (5%) with schistosomiasis. None of the 27 subjects infected with intestinal nematodes was found positive at this test. The ELISA is meant to be a pan-filarial assay, and reacted extensively with cases of M. perstans (95%), as expected, and also in 11/18 (61.1%) patients with strongyloidiasis and in 3/5 (60%) with hookworm infection. The RDT and the ELISA are both highly sensitive for the diagnosis of loiasis. The main difference lies in the extent of cross-reactivity with other parasites. Considering that the RDT is specifically meant for Loa loa infection, and its high sensitivity, this test could be a useful tool for the diagnosis of occult loiasis.

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“…However, a single dose of albendazole (400 mg) and ivermectin (150-200 µg/kg) combined and each drug alone revealed low efficacies [242]. To treat the endosymbiotic Wolbachia bacteria, doxycycline began to be used as a promising alternative drug since the 2010s, alone or in combination with anthelmintics [237,243,244].…”

Section: Mansonellosismentioning

confidence: 99%

Albendazole and Mebendazole as Anti-Parasitic and Anti-Cancer Agents: an Update

2021

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The use of albendazole and mebendazole, i.e., benzimidazole broad-spectrum anthelmintics, in treatment of parasitic infections, as well as cancers, is briefly reviewed. These drugs are known to block the microtubule systems of parasites and mammalian cells leading to inhibition of glucose uptake and transport and finally cell death. Eventually they exhibit ovicidal, larvicidal, and vermicidal effects on parasites, and tumoricidal effects on hosts. Albendazole and mebendazole are most frequently prescribed for treatment of intestinal nematode infections (ascariasis, hookworm infections, trichuriasis, strongyloidiasis, and enterobiasis) and can also be used for intestinal tapeworm infections (taeniases and hymenolepiasis). However, these drugs also exhibit considerable therapeutic effects against tissue nematode/cestode infections (visceral, ocular, neural, and cutaneous larva migrans, anisakiasis, trichinosis, hepatic and intestinal capillariasis, angiostrongyliasis, gnathostomiasis, gongylonemiasis, thelaziasis, dracunculiasis, cerebral and subcutaneous cysticercosis, and echinococcosis). Albendazole is also used for treatment of filarial infections (lymphatic filariasis, onchocerciasis, loiasis, mansonellosis, and dirofilariasis) alone or in combination with other drugs, such as ivermectin or diethylcarbamazine. Albendazole was tried even for treatment of trematode (fascioliasis, clonorchiasis, opisthorchiasis, and intestinal fluke infections) and protozoan infections (giardiasis, vaginal trichomoniasis, cryptosporidiosis, and microsporidiosis). These drugs are generally safe with few side effects; however, when they are used for prolonged time (>14-28 days) or even only 1 time, liver toxicity and other side reactions may occur. In hookworms, Trichuris trichiura, possibly Ascaris lumbricoides, Wuchereria bancrofti, and Giardia sp., there are emerging issues of drug resistance. It is of particular note that albendazole and mebendazole have been repositioned as promising anti-cancer drugs. These drugs have been shown to be active in vitro and in vivo (animals) against liver, lung, ovary, prostate, colorectal, breast, head and neck cancers, and melanoma. Two clinical reports for albendazole and 2 case reports for mebendazole have revealed promising effects of these drugs in human patients having variable types of cancers. However, because of the toxicity of albendazole, for example, neutropenia due to myelosuppression, if high doses are used for a prolonged time, mebendazole is currently more popularly used than albendazole in anti-cancer clinical trials.

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The Efficacy of Doxycycline Treatment on Mansonella perstans Infection: An Open-Label, Randomized Trial in Ghana

Cited by 35 publications

References 39 publications

Corallopyronin A for short-course anti-wolbachial, macrofilaricidal treatment of filarial infections

Corallopyronin A for short-course anti-wolbachial, macrofilaricidal treatment of filarial infections

Performance of two serodiagnostic tests for loiasis in a Non-Endemic area

Albendazole and Mebendazole as Anti-Parasitic and Anti-Cancer Agents: an Update

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