In a nutshell
- The Problem: Onchocerciasis (also known as river blindness) can lead to blindness and severe, debilitating skin irritation.
- The Program: Mass drug administration of ivermectin 1 or 2 times annually (for 10-20 years) to control or eliminate onchocerciasis.
- Track record: High-quality evaluations have demonstrated that ivermectin is effective in suppressing the worms that cause onchocerciasis. However, there is little rigorous direct evidence that ivermectin, alone, reduces rates of blindness or skin disease.
- Cost-effectiveness: Available estimates imply that this program is highly cost-effective, with $100 preventing a total of 10-50 years of serious debilitation (blindness, low vision, or irritating skin disease). However, this estimate should be interpreted with extreme caution due to the relative scarcity of data on onchocerciasis.
- Bottom line: Ivermectin is likely effective against onchocerciasis, though evidence of an effect on debilitating outcomes is not conclusive.
Table of Contents
Basics of the program
What is the program? What problem does it target?
Onchocerciasis can cause blindness, vision impairment, and skin disease (more at our writeup on onchocerciasis). The World Health Organization recommends annual treatments with ivermectin to control the disease,1 the method currently employed by the two major multilateral efforts to control the disease: the African Programme for Onchocerciasis Control (APOC) and the Onchocerciasis Elimination Programme for the Americas (OEPA).2
What are the components required to implement this program - how does it work?
This program requires ivermectin and a means of distributing it as widely and efficiently as possible. Merck, a manufacturer of ivermectin (under the brand name Mectizan) has committed to donate the drug for as long as needed.3
Distribution is generally accomplished through an approach known as community-directed treatment with ivermectin (CDTI), in which communities direct the process and agree on how the drugs will be collected from the supplier, when and how they'll be distributed, and who will be responsible for distribution and monitoring. Health workers supervise the process.4
Program track record
Micro evidence: Has this program been rigorously evaluated and shown to work?
A Cochrane review asserts that mass treatment with ivermectin has been shown to effectively and significantly reduce infection rates in flies and humans.5 Another review reports that community trials of treatment with ivermectin are associated with "a major reduction in vector infectivity but still significant residual transmission after treatment (Remme et al. 1989a) and a subsequent increase in infectivity levels to near pretreatment levels 12 months later."6 It concludes that ivermectin likely reduces infection and morbidity from onchocerciasis but that treatment may be required indefinitely.7
However, the Cochrane review mentioned above raises questions about ivermectin's impact on morbidity. It evaluated 5 trials including 3,810 participants and concluded that "questions about the effectiveness of ivermectin in preventing visual acuity loss have not been answered by best-available evidence."8
(More on our interpretation of "micro evidence" and evaluation quality.)
Macro evidence: Has this program played a role in large-scale success stories?
We have identified no such success stories. (More on the general idea of "macro evidence".)
Recommendations and concerns
What are the potential downsides of the intervention?
- The Disease Control Priorities in Developing Countries report mentions that drug resistance is a possibility.9
- Ivermectin causes some adverse reactions, but they are normally mild.10
We have not done thorough cost-effectiveness analysis of this program. Because such analysis is highly time-consuming - and because the results can vary significantly depending on details of the context - we generally do not provide cost-effectiveness analysis for an intervention unless we find what we consider to be a strong associated giving opportunity.
We provide some preliminary figures based on the Disease Control Priorities in Developing Countries report, which we previously used for cost-effectiveness estimates until we vetted its work in 2011, finding major errors that raised general concerns.
Cost-effectiveness estimates depend heavily on questions about the long-term effectiveness of ivermectin to eliminate onchocerciasis. The Disease Control Priorities in Developing Countries report provides estimates of $711 and $4012 per disability-adjusted life-year (DALY) averted for this program. These figures would place it among the more cost-effective programs.13 (More on the DALY metric.)
Using a simple conversion calculation, we estimate that $100 prevents 2.5-14 years of blindness and an additional 3.5-20 years of irritating skin disease and an additional 3-17 years of impaired vision. These numbers should be interpreted with particular caution due to the relative scarcity of data on onchocerciasis.14
- Cao, Wu-chun, et al. 1997. Ivermectin for the chemotherapy of bancroftian filariasis: A metaanalysis of the effect of single treatment. Tropical Medicine and International Health 2: 393–403. Summary available at http://www.ncbi.nlm.nih.gov/pubmed/9171850 (accessed April 23, 2010). Archived by WebCite® at http://www.webcitation.org/5pClr7UVv.
- Copenhagen Concensus Center. Copenhagen Consensus 2008 - Results (PDF).
- Ejere, Henry O.D., Ellen Schwartz and Richard Wormald. 2001. Ivermectin for onchocercal eye disease (river blindness). Cochrane Database of Systematic Reviews 2001, Issue 2. Summary available at http://www.cochrane.org/reviews/en/ab002219.html (accessed April 23, 2010). Archived by WebCite® at http://www.webcitation.org/5pDMscN2j.
- GiveWell. Website:
- Jamison, Dean T., et al., eds. 2006. Disease control priorities in developing countries (PDF). 2nd ed. New York: Oxford University Press.
- Merck. Mectizan® donation program. http://www.merck.com/corporate-responsibility/access/access-developing-… (accessed April 23, 2010). Archived by WebCite® at http://www.webcitation.org/5pCnbXz18.
- Ottesen, Eric A., et al. 2008. The Global Programme to Eliminate Lymphatic Filariasis: Health impact after 8 years (PDF). PLoS Negl Trop Dis 2: e317.
- Remme, Jan H.F. 2004. Research for control: The onchocerciasis experience. Tropical Medicine and International Health 9: 243–254.
- World Health Organization. Onchocerciasis (river blindness). http://www.who.int/blindness/causes/priority/en/index3.html (accessed April 23, 2010). Archived by WebCite® at http://www.webcitation.org/5pDNAt3CD.
"Much progress has been made in fighting the disease in several countries through control of the blackfly, however, the disease can now also be treated with an annual dose of the drug ivermectine, Mectizan®, which also relieves the severe skin itching caused by the disease." World Health Organization, "Onchocerciasis (River Blindness)."
"Ivermectin is currently employed by the African Programme for Onchocerciasis Control (APOC) and the Onchocerciasis Elimination Programme for the Americas (OEPA) for mass treatment in hyper and meso-endemic communities." Ejere, Schwartz, and Wormald 2001, Pg 4.
"In 1987, Merck announced that it would donate Mectizan® (ivermectin), our breakthrough medicine for the treatment of onchocerciasis, to all who needed it, for as long as needed." Merck, "Mectizan® Donation Program."
"APOC uses an approach referred to as community-directed treatment with ivermectin, whereby local communities rather than health services direct the treatment process (Amazigo and others 2002). A community decides collectively whether it wants ivermectin treatment, how it will collect ivermectin tablets from the medical supply entity, when and how the tablets will be distributed, who will be responsible for distribution and recordkeeping, and how the community will monitor the process. Health workers provide only the necessary training and supervision. To date, communities have responded enthusiastically to this approach (Seketeli and others 2002), and interest is now growing in exploring this strategy for interventions against other diseases (Homeida and others 2002)." Jamison et al. 2006, Pgs 440-1.
"It has been shown that distribution of ivermectin to 60% of the population results in a 70% to 75% post-treatment reduction in infected flies (Remme 1990). Similarly, mass treatment with ivermectin has been shown to be associated with a 94% reduction in the number of flies with developing infective larvae (Trpis 1990). Repeated annual treatment with ivermectin in Liberia was shown to reduce the incidence of new infections in untreated children by about 40% in the second year (Taylor 1990)." Ejere, Schwartz, and Wormald 2001, Pg 4.
Remme 2004, Pg 246.
"Treatment may need to continue indefinitely in hyper-endemic areas (Remme et al. 1990). However, because ivermectin treatment resulted in a major reduction in microfilarial loads in the human population, it was predicted that sustained annual treatment would be able to control onchocercal morbidity and eliminate the disease as a public health problem." Remme 2004, Pg 246.
Ejere, Schwartz, and Wormald 2001, Pg 2.
"Another risk is drug resistance. The control programs rely on just a few drugs, and even though drug resistance is not currently apparent, if it were to emerge, the essential tools for control would be lost. Hence, although elimination is in sight, the battle has not yet been won, and research to develop new and improved interventions and strategies for these tropical diseases remains important." Jamison et al. 2006, Pg 446.
"Higher doses of ivermectin showed greater clearance effects and maintained lower microfilaraemia levels for a longer time. The adverse reactions caused by the drug were flu-like, transient, generally mild and well tolerated by patients." Cao 1997, Pg 393.
Jamison et al. 2006, Pg 445, Table 22.3. Their methodology: "To estimate the approximate cost per DALY averted, we considered the burden of disease and treatment with ivermectin in APOC countries. Using the latest epidemiological mapping data, we estimate that, in 1995, 34.6 million people were infected in APOC countries and that 1.86 million DALYs were lost. Currently more than 44 percent of those infected are covered by community-directed treatment with ivermectin, and expectations are that treatment will be expanded to cover most of the remainder before the end of APOC in 2010.
Information from areas where ivermectin treatment has been in effect for more than 15 years shows that the prevalence and intensity of onchocerciasis infection have fallen to low levels (Borsboom and others 2003), and computer simulations predict that the disease could not become a public health problem again for at least another 10 to 20 years if treatment were halted (Remme, Alley, and Plaisier 1995). We therefore estimate that 15 years of ivermectin treatment at 65 percent coverage will prevent at least 25 years of onchocercal disease. If we assume that 70 percent of endemic communities will ultimately be covered by community-directed treatment with ivermectin and that 80 percent of those communities will maintain annual treatment at 65 percent coverage for at least 15 years, at least 26 million DALYs would be prevented over a 25-year period.
The predicted cost of community-directed treatment with ivermectin in APOC countries is US$145 million by the international donor community plus US$64 million by ministries of health and collaborating nongovernmental organizations, giving a total of US$209 million. Therefore we estimate that the cost of community-directed treatment is approximately US$7 per DALY averted." Jamison et al. 2006, Pg 444.
Jamison et al. 2006, Pg 954, Table 50.1.
See Jamison et al. 2006, Pgs 41-42, Figures 2.2 and 2.3 for a chart of the cost-effectiveness range (measured in cost per DALY) for many programs.
Though the Global Program to Eliminate Lymphatic Filariasis is relatively well-tracked, "GPELF's impact on improving OSD [onchocercal skin disease] is not yet quantified, but it can be defined once the number of individuals with onchocerciasis who live in the expanded treatment areas is more well understood." Ottesen et al. 2008.