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The large-scale control of human onchocerciasis ("river blindness") using ivermectin (Mectizan) is based largely on the drug’s ability to eliminate microfilariae rapidly from the skin without causing clinically-significant side effects.1 Depending on the specific goals of the campaign, annual treatment can be used to prevent skin and ocular morbidity,2 and biannual treatment (6-month intervals) can be used to reduce transmission of Onchocerca volvulus L3s to the point that elimination of new infections occur.3 Studies in Latin America (Guatemala) and Africa (Cameroon) also have shown that ivermectin becomes macrofilaricidal when given repetitively at 3- or 6-month intervals over a 2- to 3-year period.4–6 Here, we further analyze and compare the data from these three reports and show that when ivermectin is given on a quarterly basis (4x/yr) or biannual basis (2x/yr) to persons receiving treatment residing within a community where a high proportion of members also receives biannual treatments, new infections are prevented and elimination of adult worms accelerated.
Three key aspects of adult worm biology—live females, live males, fertile females—were first compared in individuals receiving 4x/yr treatment where (a) community level drug treatment at 6-month intervals was also ongoing7 or (b) there was no community-wide drug treatment or vector control.5 These three aspects were considered comparable between the two studies because the viability and reproductive status of the adult worms in the two locations were similar at the beginning of each trial, the ivermectin treatment regimen was the same (150 µg/kg every 3 months), the parasite material was prepared and evaluated in the same way (fixation of nodules, histologic sectioning, and H&E staining), and the same person evaluated the slides in both studies.
When persons receiving Mectizan at 3-month intervals resided in a community whose other occupants were being treated biannually, there was a strong and persistent macrofilaricidal effect over 3 years, resulting in a decline in live adult worms of 70% (females) to 78% (males) (Table 1
). Production of microfilariae by female worms exposed to 4x/yr treatment in that environment ceased after 2 years (Table 1: fertile females following 8x trt = 0). In the situation where neither vector control nor Mectizan chemotherapy was available, adult worm numbers in subjects treated 4x/yr decreased by 28% (females) and 11% (males) after 3 years. These figures represent differences between the two situations of 42% and 67%, respectively. After 3 years of 4x/yr treatment where there was no community level control, 19% of female worms were still producing microfilariae (Table 1).
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). These data are quite similar to recently published field observations in Mexico, Guatemala, and Ecuador where 80–86% of nodules examined lacked an adult male worm, and female insemination rates were quite low (< 20%) after long-term semiannual treatments.9 Interestingly, based on the linear mortality trend of female worms when individuals receive 4x/yr treatments in biannually treated communities (regression: r2 = 0.96; Figure 1), extinction of the population is predicted to occur in less than 6 years. In the absence of biannual community-wide treatment, however, parasite persistence in the treated subjects was nonlinear (regression: r2 = 0.46). The former approximation is important for future control strategies because it differs markedly from a recent estimate in which the life span of adult worms was expected to extend for 16 years when communities were treated twice a year.10 That estimate, however, was based on natural attrition with no drug effect and the unreplenished adult population dying from old age over a 12-year period.
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). Although the original data for these two groups were collected at different times and used different methods of analysis (collagenase extraction of adult worms for the 2x/yr treatment versus H&E slide examination for the 4x/yr group), we believe that they are validly comparable because an earlier study indicated that the ratio of female to male worms found with both techniques did not differ.11 Although the viability of adult female worms was similar for persons receiving 4x/yr or 2x/yr treatments within a community undergoing biannual treatments, after 24 months, the mean number of males per nodule dropped by 79% (4x/yr), compared with 44% (2x/yr); at 4x/yr, the number of female worms producing microfilariae per nodule reached zero (100% reduction) at 24 months, compared with an 82% reduction at 2x/yr. Nevertheless, if 2x/yr treatments were to continue, it is predicted that live female worms would be eliminated before Year 7 (13 treatments; regression: r2 = 0.96; Figure 1) versus elimination just after Year 5 when treatments are given at quarterly intervals (21 treatments; regression: r2 = 0.96; Figure 1). The successful control of onchocerciasis in Ecuador when biannual treatments were given over a 6-year period at a high coverage rate reinforces the likelihood that this could be the case; that is, complete reduction of skin microfilariae with elimination of transmission followed by no discernable nodules in a sentinel population.12
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). This appears not to be the case in an "open" system (ongoing transmission) where the infection may continue indefinitely5 (Figure 1). As such, this suggests that 4x/yr community-wide treatment may be the optimum regimen to attain parasite elimination within a short, logistically feasible period of time. Treatment at 2x/yr, however, may achieve essentially the same result with fewer treatments but require an additional 1–2 years.
Received June 27, 2005. Accepted for publication August 10, 2005.
* Address correspondence to Eddie W. Cupp, Department of Entomology and Plant Pathology, 301 Funchess Hall, Auburn University, Auburn, AL 36849-5413. E-mail: cupped{at}auburn.edu 
Authors’ addresses: Eddie W. Cupp and Mary S. Cupp, Department of Entomology and Plant Pathology, 301 Funchess Hall, Auburn University, Auburn, AL 36849-5413, Telephone: 334-844-5010, Fax: 334-844-5005, E-mail: cupped{at}auburn.edu and cuppmar{at}auburn.edu.
Reprint requests: Dr. Eddie W. Cupp, Department of Entomology and Plant Pathology, 301 Funchess Hall, Auburn University, Auburn, AL 36849-5413.
This article has been cited by other articles:
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  F. O. Richards Jr., J. Amann, B. Arana, G. Punkosdy, R. Klein, C. Blanco, B. Lopez, C. Mendoza, A. Dominguez, J. Guarner, et al. No Depletion of Wolbachia from Onchocerca volvulus after a Short Course of Rifampin and/or Azithromycin Am J Trop Med Hyg, November 1, 2007; 77(5): 878 - 882. [Abstract] [Full Text] [PDF]
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