A. Hoerauf | Rheinische Friedrich-Wilhelms-Universität Bonn (original) (raw)

Papers by A. Hoerauf

Research paper thumbnail of Repurposing of approved drugs from the human pharmacopoeia to target Wolbachia endosymbionts of onchocerciasis and lymphatic filariasis

International Journal for Parasitology: Drugs and Drug Resistance, 2014

Lymphatic filariasis and onchocerciasis are debilitating diseases caused by parasitic filarial ne... more Lymphatic filariasis and onchocerciasis are debilitating diseases caused by parasitic filarial nematodes infecting around 150 million people throughout the tropics with more than 1.5 billion at risk. As with other neglected tropical diseases, classical drug-discovery and development is lacking and a 50 year programme of macrofilaricidal discovery failed to deliver a drug which can be used as a public health tool. Recently, antibiotic targeting of filarial Wolbachia, an essential bacterial symbiont, has provided a novel drug treatment for filariasis with macrofilaricidal activity, although the current gold-standard, doxycycline, is unsuitable for use in mass drug administration (MDA). The anti-Wolbachia (A·WOL) Consortium aims to identify novel anti-Wolbachia drugs, compounds or combinations that are suitable for use in MDA. Development of a Wolbachia cell-based assay has enabled the screening of the approved human drug-pharmacopoeia (∼2600 drugs) for a potential repurposing. This screening strategy has revealed that approved drugs from various classes show significant bacterial load reduction equal to or superior to the gold-standard doxycycline, with 69 orally available hits from different drug categories being identified. Based on our defined hit criteria, 15 compounds were then selectively screened in a Litomosoides sigmodontis mouse model, 4 of which were active. These came from the tetracycline, fluoroquinolone and rifamycin classes. This strategy of repurposing approved drugs is a promising development in the goal of finding a novel treatment against filariasis and could also be a strategy applicable for other neglected tropical diseases.

Research paper thumbnail of Mass drug treatment for lymphatic filariasis and onchocerciasis

Trends in Parasitology, 2003

This review summarizes the progress towards control of lymphatic filariasis (LF) and onchocercias... more This review summarizes the progress towards control of lymphatic filariasis (LF) and onchocerciasis, focussing on the impact of mass drug administration (MDA) programmes, in particular those that have developed following the donation of ivermectin and ...

Research paper thumbnail of Corallopyronin A Specifically Targets and Depletes Essential Obligate Wolbachia Endobacteria From Filarial Nematodes In Vivo

Journal of Infectious Diseases, 2012

Research paper thumbnail of Tetracycline therapy targets intracellular bacteria in the filarial nematode Litomosoides sigmodontis and results in filarial infertility

Journal of Clinical Investigation, 1999

Research paper thumbnail of Filariasis in Africa-treatment challenges and prospects

Clinical Microbiology and Infection, 2011

Lymphatic filariasis (LF) and onchocerciasis are parasitic nematode infections that are responsib... more Lymphatic filariasis (LF) and onchocerciasis are parasitic nematode infections that are responsible for a major disease burden in the African continent. Disease symptoms are induced by the immune reactions of the host, with lymphoedema and hydrocoele in LF, and dermatitis and ocular inflammation in onchocerciasis. Wuchereria bancrofti and Onchocerca volvulus, the species causing LF and onchocerciasis in Africa, live in mutual symbiosis with Wolbachia endobacteria, which cause a major part of the inflammation leading to symptoms and are antibiotic targets for treatment. The standard microfilaricidal drugs ivermectin and albendazole are used in mass drug administration programmes, with the aim of interrupting transmission, with a consequent reduction in the burden of infection and, in some situations, leading to regional elimination of LF and onchocerciasis. Co-endemicity of Loa loa with W. bancrofti or O. volvulus is an impediment to mass drug administration with ivermectin and albendazole, owing to the risk of encephalopathy being encountered upon administration of ivermectin. Research into new treatment options is exploring several improved delivery strategies for the classic drugs or new antibiotic treatment regimens for anti-wolbachial chemotherapy.

Research paper thumbnail of A Randomized, Double-Blind Clinical Trial of a 3-Week Course of Doxycycline plus Albendazole and Ivermectin for the Treatment of Wuchereria bancrofti Infection

Clinical Infectious Diseases, 2006

Eight-and 6-week courses of doxycycline are superior to standard treatment of bancroftian filaria... more Eight-and 6-week courses of doxycycline are superior to standard treatment of bancroftian filariasis. Standard treatment (albendazole plus ivermectin) is associated with adverse reactions. We assessed whether a shorter (i.e, 3-week) course of doxycycline with standard treatment would show superior efficacy to standard treatment alone and reduce the incidence of adverse reactions.

Research paper thumbnail of Elimination of African onchocerciasis: modeling the impact of increasing the frequency of ivermectin mass treatment

PloS one, 2014

The African Programme for Onchocerciasis Control (APOC) is currently shifting its focus from morb... more The African Programme for Onchocerciasis Control (APOC) is currently shifting its focus from morbidity control to elimination of infection. To enhance the likelihood of elimination and speed up its achievement, programs may consider to increase the frequency of ivermectin mass treatment from annual to 6-monthly or even higher. In a computer simulation study, we examined the potential impact of increasing the mass treatment frequency for different settings. With the ONCHOSIM model, we simulated 92,610 scenarios pertaining to different assumptions about transmission conditions, history of mass treatment, the future mass treatment strategy, and ivermectin efficacy. Simulation results were used to determine the minimum remaining program duration and number of treatment rounds required to achieve 99% probability of elimination. Doubling the frequency of treatment from yearly to 6-monthly or 3-monthly was predicted to reduce remaining program duration by about 40% or 60%, respectively. Th...

Research paper thumbnail of Repurposing of approved drugs from the human pharmacopoeia to target Wolbachia endosymbionts of onchocerciasis and lymphatic filariasis

International Journal for Parasitology: Drugs and Drug Resistance, 2014

Lymphatic filariasis and onchocerciasis are debilitating diseases caused by parasitic filarial ne... more Lymphatic filariasis and onchocerciasis are debilitating diseases caused by parasitic filarial nematodes infecting around 150 million people throughout the tropics with more than 1.5 billion at risk. As with other neglected tropical diseases, classical drug-discovery and development is lacking and a 50 year programme of macrofilaricidal discovery failed to deliver a drug which can be used as a public health tool. Recently, antibiotic targeting of filarial Wolbachia, an essential bacterial symbiont, has provided a novel drug treatment for filariasis with macrofilaricidal activity, although the current gold-standard, doxycycline, is unsuitable for use in mass drug administration (MDA). The anti-Wolbachia (A·WOL) Consortium aims to identify novel anti-Wolbachia drugs, compounds or combinations that are suitable for use in MDA. Development of a Wolbachia cell-based assay has enabled the screening of the approved human drug-pharmacopoeia (∼2600 drugs) for a potential repurposing. This screening strategy has revealed that approved drugs from various classes show significant bacterial load reduction equal to or superior to the gold-standard doxycycline, with 69 orally available hits from different drug categories being identified. Based on our defined hit criteria, 15 compounds were then selectively screened in a Litomosoides sigmodontis mouse model, 4 of which were active. These came from the tetracycline, fluoroquinolone and rifamycin classes. This strategy of repurposing approved drugs is a promising development in the goal of finding a novel treatment against filariasis and could also be a strategy applicable for other neglected tropical diseases.

Research paper thumbnail of Mass drug treatment for lymphatic filariasis and onchocerciasis

Trends in Parasitology, 2003

This review summarizes the progress towards control of lymphatic filariasis (LF) and onchocercias... more This review summarizes the progress towards control of lymphatic filariasis (LF) and onchocerciasis, focussing on the impact of mass drug administration (MDA) programmes, in particular those that have developed following the donation of ivermectin and ...

Research paper thumbnail of Corallopyronin A Specifically Targets and Depletes Essential Obligate Wolbachia Endobacteria From Filarial Nematodes In Vivo

Journal of Infectious Diseases, 2012

Research paper thumbnail of Tetracycline therapy targets intracellular bacteria in the filarial nematode Litomosoides sigmodontis and results in filarial infertility

Journal of Clinical Investigation, 1999

Research paper thumbnail of Filariasis in Africa-treatment challenges and prospects

Clinical Microbiology and Infection, 2011

Lymphatic filariasis (LF) and onchocerciasis are parasitic nematode infections that are responsib... more Lymphatic filariasis (LF) and onchocerciasis are parasitic nematode infections that are responsible for a major disease burden in the African continent. Disease symptoms are induced by the immune reactions of the host, with lymphoedema and hydrocoele in LF, and dermatitis and ocular inflammation in onchocerciasis. Wuchereria bancrofti and Onchocerca volvulus, the species causing LF and onchocerciasis in Africa, live in mutual symbiosis with Wolbachia endobacteria, which cause a major part of the inflammation leading to symptoms and are antibiotic targets for treatment. The standard microfilaricidal drugs ivermectin and albendazole are used in mass drug administration programmes, with the aim of interrupting transmission, with a consequent reduction in the burden of infection and, in some situations, leading to regional elimination of LF and onchocerciasis. Co-endemicity of Loa loa with W. bancrofti or O. volvulus is an impediment to mass drug administration with ivermectin and albendazole, owing to the risk of encephalopathy being encountered upon administration of ivermectin. Research into new treatment options is exploring several improved delivery strategies for the classic drugs or new antibiotic treatment regimens for anti-wolbachial chemotherapy.

Research paper thumbnail of A Randomized, Double-Blind Clinical Trial of a 3-Week Course of Doxycycline plus Albendazole and Ivermectin for the Treatment of Wuchereria bancrofti Infection

Clinical Infectious Diseases, 2006

Eight-and 6-week courses of doxycycline are superior to standard treatment of bancroftian filaria... more Eight-and 6-week courses of doxycycline are superior to standard treatment of bancroftian filariasis. Standard treatment (albendazole plus ivermectin) is associated with adverse reactions. We assessed whether a shorter (i.e, 3-week) course of doxycycline with standard treatment would show superior efficacy to standard treatment alone and reduce the incidence of adverse reactions.

Research paper thumbnail of Elimination of African onchocerciasis: modeling the impact of increasing the frequency of ivermectin mass treatment

PloS one, 2014

The African Programme for Onchocerciasis Control (APOC) is currently shifting its focus from morb... more The African Programme for Onchocerciasis Control (APOC) is currently shifting its focus from morbidity control to elimination of infection. To enhance the likelihood of elimination and speed up its achievement, programs may consider to increase the frequency of ivermectin mass treatment from annual to 6-monthly or even higher. In a computer simulation study, we examined the potential impact of increasing the mass treatment frequency for different settings. With the ONCHOSIM model, we simulated 92,610 scenarios pertaining to different assumptions about transmission conditions, history of mass treatment, the future mass treatment strategy, and ivermectin efficacy. Simulation results were used to determine the minimum remaining program duration and number of treatment rounds required to achieve 99% probability of elimination. Doubling the frequency of treatment from yearly to 6-monthly or 3-monthly was predicted to reduce remaining program duration by about 40% or 60%, respectively. Th...