ABSTRACT
The decision in 1987 by the pharmaceutical firm Merck & Co. to provide Mectizan (ivermectin) free of charge to river blindness control programs has challenged the international public health community to find effective ways to distribute the drug to rural populations most affected by onchocerciasis. In the Americas, PAHO responded to that challenge by calling for the elimination of all morbidity from onchocerciasis from the Region by the year 2007 through mass distribution of ivermectin. Since 1991, a multinational, multiagency partnership (consisting of PAHO, the endemic countries, nongovernmental development organizations, the Centers for Disease Control and Prevention in Atlanta, Georgia, as well as academic institutions and funding agencies) has developed the political, financial, and technical support needed to move toward the realization of that goal. This partnership is embodied in the Onchocerciasis Elimination Program for the Americas (OEPA), which is supported by the River Blindness Foundation (RBF) and now by the Carter Center. OEPA was conceived as a means of maintaining a regional initiative to eliminate what is otherwise a low priority disease. Since its inception in 1993, the OEPA has provided more than US$2 million in financial, managerial, and technical assistance to stimulate and/or support programs in Brazil, Colombia, Ecuador, Guatemala, Mexico and Venezuela, so as to take full advantage of the Merck donation. Now halfway into a five-year, US$ 4 million grant provided through the Inter-American Development Bank, the OEPA's capacity to support the regional initiative is assured through 1999
Subject(s)
Onchocerciasis , Ivermectin/pharmacology , Economic Cooperation , Technical Cooperation , Rural Population , Health Policy , Latin AmericaABSTRACT
The clinical investigations with three types of a three days regimen of amocarzine permitted to adjust the fixed dosing to the body weight related dosing and subsequently the adminstration of amocarzine from fasting state to drug intake after food. The main objective to reach a dose woth predictable and sustained absorption was achieved, and this in turn proved to be onchocercacidal and safe. A combined clinicopharmacokinetic study showed enhancement and consistency of amocarzine absorption after food. Quantitative assessment of the urinary excretion confirmed presence of the N-oxide metabolite, which qualitatively was visible by a urine colorimetry. This assay proved useful for drug monitoring. Ultrasonography of onchocercal skin nodules detected changes within the nodules following amocarzine therapy. Histology agter nodul-ectomy at four months post-therapy showed thal 57% of the female worms were dead, 24% necrobiotic, and 19% alive; male worms were more necrobiotic. Skin microfilariae were reduced within one week to about 10% of the initial level and after one year they remained at about 20%. Skin punch biopsies on day 5 showed that most microfilariae were dead or moribund. Ocular reduction of microfilariae was also observed, althought it was slower than in the skin. The visual acuity improved within the one year's observation time. Ocular and clinical tolerability was good, with one exception of neurological disturbance, which was fully reversible. Se quential testing of the liver function showed average values within the normal range. In conclusion, a repeat low dose regimen of amocarzine (3 mg/Kg twice daily postprandially for three consecutive days) was well absorbed with predictable plasma levels, macro-and microfilaricidal with good local and systemic tolerability in patients with moderate to heavy onchocerciasis. Amorcarzine is recommended for further clinical investigations, particularly inf emales and juveniles. Urine colorimetry and nodular ultrasonography are recommended for optional monitoring of amocarzine