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Onchocerciasis treatment is one of the most positive stories in tropical medicine although major challenges remain to reaching the ultimate goal of disease elimination. Such challenges are to be expected when the therapeutic goal is to kill and safely remove a large multistage, efficient, metazoan infectious agent such as Onchocerca volvulus that has an exceptionally complicated relationship with its host. Successful control of onchocerciasis has often been hampered by host reactions following chemotherapy, that can sometimes cause significant tissue pathology. Presence of other filariae, particularly Loa loa, in endemic onchocerciasis-treatment areas also poses severe problems due to adverse reactions caused by drug-induced death of the coincident microfilariae of this usually clinically benign species. Although ivermectin has been very successful, there is a need to enhance the progress toward elimination of onchocerciasis; new drugs and their efficient use are keys to this. The permanent absence of Onchocerca microfilaridermia, defined as the lack of resurgence of skin microfilarial loads after treatment, is the ultimate characteristic of a useful new chemotherapeutic agent. Several drugs are under investigation to achieve this, including the reassessment of currently available and previously tested agents, such as the antibiotic, doxycycline, which targets the adult parasites through its anti-Wolbachia endosymbiont activity. Flubendazole, a benzimidazole derivative approved for treatment of human gastrointestinal nematodes, is also being considered for repurposing as a macrofilaricide to aid in the achievement of eradication. The managerial challenges existing at the population level also need to be addressed; these include drug-distribution fatigue, the need to include noncompliant people, civil unrest in endemic areas, political cross-border issues, restrictions of age and pregnancy, and complications due to integration with other treatment programs. It is likely that a panel of chemotherapeutic options, ...

Tarig B Higazi,1 Timothy G Geary,2 Charles D Mackenzie3,41Department of Biological Sciences, Ohio University Zanesville, Zanesville, OH, USA; 2Institute of Parasitology, McGill University, Montreal, QC, Canada; 3Center for Neglected Tropical Diseases, Liverpool School of Tropical Medicine, Liverpool, UK; 4Department of Pathobiology & Diagnostic Investigation, Michigan State University, East Lansing, MI, USAAbstract: Onchocerciasis treatment is one of the most positive stories in tropical medicine although major challenges remain to reaching the ultimate goal of disease elimination. Such challenges are to be expected when the therapeutic goal is to kill and safely remove a large multistage, efficient, metazoan infectious agent such as Onchocerca volvulus that has an exceptionally complicated relationship with its host. Successful control of onchocerciasis has often been hampered by host reactions following chemotherapy, that can sometimes cause significant tissue pathology. Presence of other filariae, particularly Loa loa, in endemic onchocerciasis-treatment areas also poses severe problems due to adverse reactions caused by drug-induced death of the coincident microfilariae of this usually clinically benign species. Although ivermectin has been very successful, there is a need to enhance the progress toward elimination of onchocerciasis; new drugs and their efficient use are keys to this. The permanent absence of Onchocerca microfilaridermia, defined as the lack of resurgence of skin microfilarial loads after treatment, is the ultimate characteristic of a useful new chemotherapeutic agent. Several drugs are under investigation to achieve this, including the reassessment of currently available and previously tested agents, such as the antibiotic, doxycycline, which targets the adult parasites through its anti-Wolbachia endosymbiont activity. Flubendazole, a benzimidazole derivative approved for treatment of human gastrointestinal nematodes, is also being considered for repurposing as a macrofilaricide to aid in the achievement of eradication. The managerial challenges existing at the population level also need to be addressed; these include drug-distribution fatigue, the need to include noncompliant people, civil unrest in endemic areas, political cross-border issues, restrictions of age and pregnancy, and complications due to integration with other treatment programs. It is likely that a panel of chemotherapeutic options, new and old, supported by strong and effective distribution systems will be the best way to address challenges of treatment and elimination of this infection. Future research should also address management of treatment and control, and consider how new treatment paradigms can be incorporated to meet time lines set for global elimination by 2025.Keywords: mass drug administration, ivermectin, macrofilaricides, challenges

Lymphatic filariasis (LF) is one of the most debilitating and disfiguring diseases common in Ethiopia and is caused by Wuchereria bancrofti. Mapping for LF has shown that 70 woredas (districts) are endemic and 5.9 million people are estimated to be at risk. The national government's LF elimination programme commenced in 2009 in 5 districts integrated with the onchocerciasis programme. The programme developed gradually and has shown significant progress over the past 6 years, reaching 100% geographical coverage for mass drug administration (MDA) by 2016. To comply with the global LF elimination goals an integrated morbidity management and disability prevention (MMDP) guideline and a burden assessment programme has also been developed; MMDP protocols and a hydrocoele surgical handbook produced for country-wide use. In Ethiopia, almost all LF endemic districts are co-endemic with malaria and vector control aspects of the activities are conducted in the context of malaria programme as the vectors for both diseases are mosquitoes. In order to monitor the elimination, 11 sentinel and spot-check sites have been established and baseline information has been collected. Although significant achievements have been achieved in the scale up of the LF elimination programme, there is still a need to strengthen operational research to generate programme-relevant evidence, to increase access to morbidity management services, and to improve monitoring and evaluation of the LF programme. However, the current status of implementation of the LF national programme indicates that Ethiopia is poised to achieve the 2020 goal of elimination of LF. Nevertheless, to achieve this goal, high and sustained treatment coverage and strong monitoring and evaluation of the programme are essential.