Chemotherapy in the treatment, control, and elimination of human onchocerciasis

Abstract

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.

Reaching the last mile: main challenges relating to and recommendations to accelerate onchocerciasis elimination in Africa

“…In spite of this evidence that assures that the elimination of onchocerciasis from the continent is feasible, there are challenges regarding the accomplishment of this by 2025 [44–49]. The major challenges pertaining to the elimination of onchocerciasis in Africa are:incomplete elimination mapping of all transmission zones;co-endemicity of onchocerciasis and loiasis;possible emergence of ivermectin resistance;uncoordinated cross-border elimination efforts;conflict and civil war;suboptimal program implementation; andtechnical and financial challenges.…”

“…A small focus is found at the boundary between Kenya and South Sudan. The areas with low prevalence stretch from southwest Benin to west Ethiopia, and from north Angola to central Chad [44]. Figure 2 is map of estimated prevalence of L. loa in Africa throughout history.

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“…L. loa causes ocular and systemic manifestations with minor effects on the quality of life [44]. The issue is that in areas co-endemic with onchocerciasis, ivermectin treatment of individuals harbouring high L. loa microfilariemia causes serious neurological adverse events that might lead to death [85, 90, 93–96].…”

“…There are, however, many challenges to achieve the elimination of onchocerciasis in Africa [44–49]. This review examines the key challenges related to the elimination of onchocerciasis by 2020–2025 in Africa, and proposes recommendations to overcome the challenges and accelerate disease elimination.…”

Ivermectin: enigmatic multifaceted ‘wonder’ drug continues to surprise and exceed expectations

“…40 It is increasingly believed that the rapid microfilarial clearance following ivermectin dosing results not from the direct impact of the drug but via suppression of the parasite's ability to evade the host's natural immune defense mechanism. [41][42][43][44][45][46][47][48][49] Immunomodulatory agents often display fewer side effects than drugs, as well as producing less opportunity for creation of resistance in target microorganisms, which helps explain the absence of drug resistance in humans.…”