Onchocerciasis is an important blindness-causing disease resulting from infection by the filarial parasite Onchocerca volvulus, transmitted by Simulium blackflies. An estimated 18 million persons are infected worldwide 1, and approximately 770000 are blind or visually impaired as a consequence of the infection 1. The infection also causes severe and troublesome skin disease 2 and is associated directly with increased mortality 3.

Ivermectin (Mectizan^®) is an oral microfilaricidal drug that is safe and effective for mass treatment of onchocerciasis 4 and is provided free to endemic countries by Merck & Co. The Onchocerciasis Elimination Program for the Americas (OEPA) has coordinated the distribution of ivermectin since 1991 in the six endemic countries in Latin America (Brazil, Colombia, Ecuador, Guatemala, Mexico and Venezuela) with two principal goals: to eliminate morbidity caused by onchocerciasis by 2007 and to eliminate the infection where possible using a strategy of mass treatment of endemic communities with ivermectin 5.

Elimination is a high priority to prevent new morbidity, to allow the reallocation of limited health and financial resources to other health priorities, and because of the potential for the development of parasite resistance to ivermectin in the long term 6. The development of resistance to ivermectin by O. volvulus is a serious concern because there are no safe or practical alternative treatments currently available for mass distribution in human populations. It has been suggested that the infection could be eliminated from the Americas, through twice-annual treatments with ivermectin to greater than 85% of the eligible population at risk for onchocerciasis over a period of 10–15 years, via the interruption of the transmission of infection and death of adult parasites by senescence 7.

In Ecuador, the National Program for the Elimination of Onchocerciasis has pursued a program of mass treatments with ivermectin in endemic communities over the past 14 years (1990–2003) and has achieved high rates of coverage. The Ecuadorian Program provides an important model to evaluate whether elimination of O. volvulus infection is a realistic aim for an endemic country in the Americas using an ivermectin-based treatment strategy.

The National Program for Onchocerciasis Elimination in Ecuador has used the phased introduction of mass distribution of ivermectin in endemic communities to control onchocerciasis as a public health problem since 1990. The findings of the in-depth surveys conducted in 2000 and 2004 provide some evidence that the infection has been eliminated in the sentinel communities in the Río Santiago and Río Canandé. Because of the high coverage rates achieved, it is possible that O. volvulus infection has been eliminated from the Río Santiago sub-focus and all satellite foci including the Río Canandé sub-focus. However, O. volvulus infection is still active in the hyperendemic sub-focus of the Río Cayapas as demonstrated by the presence of individuals with dermal microfilariae and infected Simulium blackflies.

Unlike foci of onchocerciasis in Africa, the foci in the Americas are geographically well defined and are amenable to focused attack that, theoretically, could lead to elimination of the infection from the continent. With this in mind, The PanAmerican Health Organization in 1991 called for the elimination of all morbidity from onchocerciasis in the Americas and where possible suppression of transmission by 2007 57.

The rationale for the current ivermectin control strategy is derived from studies conducted in Guatemala that indicated that twice-annual distribution of ivermectin to all eligible persons could suppress transmission 1920, and the results of simulation studies with a mathematical model that indicated that suppression of transmission could be achieved by treatment of at least 85% of the eligible population 7. If suppression of transmission can be maintained in an isolated focus for the reproductive life span of adult females, estimated at 13–14 years 21, the adult parasite population would die by senescence 22 and the infection would be eliminated.

We have demonstrated previously that an operational program based on ivermectin distribution twice annually over a period of 5 years in the Río Santiago sub-focus appeared to completely suppress O. volvulus transmission 11. We have now extended these findings to show that transmission of O. volvulus in the Río Santiago might have been interrupted for at least 10 years (1995–2004). There is no evidence of new onchocercal ocular morbidity in the Río Santiago and dermal microfilariae have been absent in the three sentinel communities since 1996 11. Further, studies to detect IgG4 antibodies against the O. volvulus antigen OV16 using immunochromatic cards that are highly sensitive and specific for O. volvulus infection 23 were negative in 112 children aged less than 11 years in 2001 (i.e. children born since 1990 when the first dose of ivermectin was administered; Rumbea Guzman et al, unpublished data) providing further evidence for an interruption of transmission. These data together indicate that O. volvulus infection, after at least 13 years of continuous annual or twice-annual mass treatments with ivermectin, has now been eliminated from the Río Santiago sub-focus.

O. volvulus infection remains active in the hyperendemic communities in the Río Cayapas. Individuals with dermal microfilariae were detected in three sentinel communities (total of 5 individuals) during the 2004 survey and infected blackflies were detected in two sentinel communities. Two of the three communities had received fewer ivermectin treatments than other sentinel communities having started to receive treatment in 1996 (Table 2). Microfilariae positive individuals were aged greater than 25 years and tended to have evidence of onchocercal nodules (4/5 individuals). The use of skin snips to detect O. volvulus infection in humans is relatively insensitive and it is likely that there is a larger reservoir of active infection in these communities than suggested by the skin snip results. The latter is supported by the finding of a further four individuals in the hyperendemic sentinel communities in the Río Cayapas that had negative skin tests for microfilariae but probable microfilaricidal skin reactions after ivermectin at the time of the 2004 survey. It is not clear how active is infection transmission because a serological study using the OV16 immunochromatic cards conducted in 2001 showed 2.1% (3/145) of subjects aged 0–5 years to have evidence of specific antibodies (Rumbea Guzman et al, unpublished data) although no children in this age range had positive skin snips for microfilariae. Although infection remains present, there was no evidence of new onchocercal ocular lesions in any of the sentinel communities in the Río Cayapas indicating that ocular onchocerciasis might have been eliminated as a public health problem.

All of the hyperendemic communities in the Río Cayapas have received at least 5 years of twice-annual treatments with ivermectin (Table 1) and the finding of active infection is in contrast to our previous findings of the possible complete suppression of infection in the Río Santiago after 5 years of twice-annual treatments 11 indicating possible differences in the minimum effective duration of ivermectin mass treatments required to suppress transmission between the two infection sub-foci. There are three possible explanations for this difference: (1) the predominant vector in the Río Cayapas sentinel communities, S. exiguum, has a higher vectorial capacity than S. quadrivittatum that predominates in the Río Santiago 2425; (2) the same infected individuals might refuse treatment repeatedly, or are ineligible for long periods (e.g. through repeated pregnancies), and remain an active source of transmission of O. volvulus or temporary migrations of infected individuals in and out the Río Cayapas and the failure of them to receive repeated treatments could maintain the infection reservoir (this appears an unlikely explanation as all these individuals found positive had received significant numbers of ivermectin treatments – 10/13, 6/13, 12/13, 13/13, and 11/21); and (3) a sub-population of adult female O. volvulus worms appear to respond poorly to the fertility suppressant effects of ivermectin, and this effect is observed after repeated doses 2627.

The failure to suppress infection in the Río Cayapas might indicate the need for a change in treatment strategy. Studies conducted in Cameroon and Guatemala show that treatment every 3 months with standard doses of ivermectin is safe and well-tolerated and has significant macrofilaricidal effects against adult O. volvulus 2829. In fact, histological studies of onchocercal nodules from Ecuador from individuals with a mean of only 8.2 treatments with ivermectin have shown dramatic effects on adult female viability and fertility and also marked reductions in the frequencies of male worms 30, and provided a histological picture similar to that reported in nodules collected in the Onchocerciasis Control Program area of West Africa after 9–10 years of vector control 30. These observations indicate that the period for which treatment must be maintained after suppression of infection in a community is achieved could be less than previously estimated if adult worms die or cannot maintain sexual reproduction earlier than previously estimated. It is possible that an intensive program of increased frequency of ivermectin treatment (i.e. 3-monthly) in combination with a course of doxycycline that can sterilize adult females worms 31 in skin test positive individuals and the treatment of repeated treatment refusers and migrants could yield rapid results in the suppression of transmission of O. volvulus.

The plan for certification of the elimination of onchocerciasis envisaged by OEPA comprises four phases 15: phase I – treatment coverage of greater than 85% of the population with twice-annual ivermectin treatments for a period of 2–4 years (or 4–8 rounds of treatment) causing temporary interruption of transmission; phase II – continued suppression of O. volvulus with biannual high coverage treatments with no blackflies infected with O. volvulus and no new individuals being infected (i.e. zero incidence of infection) for the lifespan of the adult female worms (e.g. 13–14 years 21); phase III – starting 12–14 years after the suppression of infection (or 14–18 years after the start of ivermectin treatments) when all adult females have died and suppression of infection is no longer dependent on ivermectin and consists of a 3 year 'surveillance' period of pre-certification during which ivermectin treatment is suspended; and phase IV – certification of elimination of the O. volvulus infection.

Our previous observations in the Río Santiago sub-focus 11 would support the time periods provided for phases I and II, but to achieve phase I in the hyperendemic area of the Río Cayapas sub-focus is likely to require much longer with the current twice-annual treatment strategy. It is likely that the periods required for each phase will vary according to the efficiency of the vector species and other factors unique to each geographic sub-focus (e.g. treatment coverage, migration patterns). Our data indicate that the Río Santiago sub-focus might be ready for the third phase of pre-certification. Pre-certification and suspension of ivermectin treatment could be considered also in Río Onzole sub-focus and satellite foci where annual or semi-annual treatments have been provided continuously for at least 13 years.

Before suspension of treatment, a survey of all endemic communities within each sub-focus should be conducted to ensure that the findings in the sentinel communities are generalizeable to non-sentinel communities. These surveys should include more sensitive diagnostic methods including the detection of O. volvulus DNA in skin snips 32 and specific antibodies using the OV16 immunochromatic cards 2333 to exclude very low-level infections and histologic analysis of the viability and fertility of female worms in onchocercal nodules (if present). Detailed vectors studies might be required to examine the flight range and dispersal patterns of Simulium blackflies from communities in the Río Cayapas where transmission persists because of the potential risk of dispersal of infected Simulium. Also required will be a study of migration to determine if there are significant migrations of potentially infected individuals from the hyperendemic communities in the Río Cayapas to the Río Santiago and vice versa. Pre-certification of these foci of infection could reduce the cost of current control activities by approximately 75% (from US $250000 to just over US $60000) and release resources for an intensive elimination strategy in the Río Cayapas sub-focus.

The National Program for Onchocerciasis Elimination in Ecuador has pioneered the use of community health workers to distribute ivermectin and the integration of ivermectin distribution within primary health care activities. The diversification of the activities of the control team and the integration of control within primary health care services has become increasingly important in maintaining high rates of coverage with ivermectin as the public health threat posed by onchocerciasis is perceived to be less and less important by the inhabitants of endemic communities. The data from this study provide evidence that an operational program in Ecuador might have eliminated ocular onchocerciasis as a public health problem and has made significant progress towards the goal of the elimination of the infection from Ecuador, and provides a model control program for the evaluation of the potential for the elimination of onchocerciasis from the Americas. The elimination of onchocerciasis from Latin America and Africa is an important health priority and the data from the current study provides evidence that an ivermectin-based treatment program could be a feasible strategy for the elimination of the infection from other foci of infection.

OEPA: Onchocerciasis Elimination Program for the Americas; MMFL: Mean microfilarial load; PCR: Polymerase chain reaction; DNA: Deoxyribonucleic acid

The author(s) declare that they have no competing interests.

JCV is the coordinator for the Programa Nacional de Eliminación de la Oncocercosis en el Ecuador and supervised the collection of blackflies. PJC is an unpaid technical consultant to the program, and drafted the manuscript and prepared it for publication. RL supervised the community treatments with ivermectin. TM is a former coordinator of the program and is an unpaid technical consultant to the program. JR and RP performed the ophthalmological examinations. AAL assisted in the collection of blackflies and performed the PCR analyses. RHG helped draft the manuscript. JRG was the Director of the Program until his death on 4 September 2006. All authors read and approved the final manuscript.