Have We Truly Conquered River Blindness?
Seventy five percent of blindness worldwide is avoidable through prevention or treatment, with 90% of these avoidable cases occurring in developing countries. Human onchocerciasis, better known as River Blindness, is a parasitic disease caused by infection with the nematode (roundworm) Onchocerca volvulus and is the world’s second-leading infectious cause of blindness. Thirty seven million people are infected with onchocerciasis worldwide. Calculations, which are likely to vastly under-represent the magnitude of the problem, indicate that 500,000 individuals have visual impairment and 270,000 are blind. It is estimated that over 130 million people are at risk of infection in West and Central Africa, and to a lesser extent Yemen and Latin America.
The parasitic worms which cause onchocerciasis are transmitted to humans through the bite of Simulium sp. flies (black flies) which breed predominantly in fast flowing white water sections of rivers. Adult O. volvulus worms can live for up to fifteen years in the human body, with the males and females entwined in nodules within the subcutaneous tissue of the skin. After mating, the female worm releases up to 1000 embryos (known as microfilariae) per day into the surrounding tissue. If left untreated, the microfilariae can live for 1–2 years, migrating to many areas of the body and in particular the eye and skin lymphatic system. When these microfilariae die they cause an inflammatory response that can lead to severe skin rashes, lesions, intense itching, skin de-pigmentation and damage to the optic nerve leading to blindness. While the initial infection can be treated, the blindness, once occurred, is irreversible.
Mass chemotherapy combined with
insecticidal spraying became the norm,
OCP covering over 1.2 million km2 and
protecting 30 million people in eleven
countries at its peak
Onchocerciasis belongs to a group of diseases called Neglected Tropical Diseases (NTDs), so named because, although they affect vast numbers of people globally, research, control and treatment is grossly under-funded and under-resourced in comparison to the burden of the disease they bestow on afflicted populations.
Although still classified as an NTD, onchocerciasis has been the focus of several large-scale control efforts since the biology and life cycle of the disease was first understood. The Onchocerciasis Control Programme (OCP) operated in West Africa during the period 1974 to 1988, exclusively targeting black fly populations through mass larvicide spraying of the flies’ breeding sites, in fast flowing rivers, from helicopters and aircrafts. In 1987, with the donation of Mectizan® (ivermectin) by Merck & Co., Inc., mass chemotherapy combined with insecticidal spraying became the norm, with the OCP covering over 1.2 million km2 and protecting 30 million people in eleven countries at its peak. The OCP was a fantastic early example of multi-disciplinary collaboration involving the World Health Organization, the World Bank, the United Nations Development Programme and the UN Food and Agriculture Organization. Specifically, it clearly demonstrated the synergistic value that comes from countries and organisations working together in partnership, as well as the economic benefits and social development that results from investments made in a disease control programme in remote and neglected areas.
Indeed, the OCP was deemed to be such a success that onchocerciasis was no longer considered a public health problem by the end of 2002, with approximately 600,000 cases of blindness prevented and 25 million hectares of land made safe for cultivation and resettlement. However, vast swathes of Africa remained untreated and onchocerciasis was still claiming the sight and disrupting the lives of hundreds of thousands of people each year.
Ivermectin does not kill the
adult worms and therefore must
be administered regularly and
consistently until transmission has
been halted and the adult worm
populations have naturally died out
Although Non Governmental Development Organizations (NGDOs) continued mass ivermectin distribution in various regions from 1989 to 1994, the OCP control zone had excluded almost 100 million people in areas of active transmission. In 1995 a second programme to combat the remaining burden of Africa’s river blindness, named the African Programme for Onchocerciasis Control (APOC), was initiated. The APOC covered an additional nineteen countries and relied mainly upon Community-Directed Treatment with Ivermectin (CDTI). Such community treatment strategies empower local people to fight river blindness in their own villages, as well as relieving suffering and slowing transmission of the disease. The programme, which has been extended until 2015, intends to treat over 90 million people annually in 19 countries while protecting an at-risk population of 115 million and aiming to prevent over 40,000 cases of blindness every year.
Community-directed treatment with ivermectin is now the mainstay for onchocerciasis control throughout West Africa and is particularly effective because it only needs to be taken annually (the strategy in Africa) or biannually (in the Americas), needs no refrigeration, and has a wide margin of safety enabling drug administration to begin in communities with only minimal training of community health workers. CDTI has therefore played a major role in alleviating current and future onchocerciasis-related health risks as well as having a direct impact on transmission. The drug itself paralyses and kills the microfilariae, temporarily halting transmission. In addition it also reduces the fecundity of the adult females, reducing microfilarial output for a number of months after treatment. However, ivermectin does not kill the adult worms and therefore must be administered regularly and consistently until transmission has been halted and the adult worm populations have naturally died out. This seemingly huge task has been greatly facilitated by Merck’s pledge to donate the drugs free of charge until onchocerciasis is eliminated. Long-term commitments, such as these, are essential elements for a programme’s sustainability.
Success Stories and Future Fears
Although river blindness is still a very real and ongoing problem, there have been success stories. The island of Bioko in the Republic of Equatorial Guinea was the only island in the world to have endemic onchocerciasis. Control of onchocerciasis, using ivermectin, began in 1990 yielding clinical benefits but did not successfully interrupt transmission. It took sustained efforts to eliminate the endemic black fly vectors (which do not exist elsewhere in Africa; and in turn mainland vectors do not re-invade) using helicopters and ground-based applications of larvicide combined with a programme of ivermectin treatment to knock back transmission, which led to the successful elimination of transmission of the disease in 2005.
On the mainland, however, things are, unsurprisingly, a lot more complex. Over a decade into the 21st century, with mass ivermectin treatment extending into its’ 23rd year, high levels of onchocerciasis transmission and infection remain problematic for many West African countries. With the cessation of OCP vector control, early predictions on how long ivermectin treatment would need to be continued to achieve the goal of removing onchocerciasis as a public health problem have not held up and active transmission is still occurring in several areas with millions of people still at risk. Indeed reinvasion of the disease has occurred in many of the OCP areas and little is known about how many additional treatments must be given in areas that have no current recorded infections, in either humans or vectors, to halt reinvasion.
Early predictions on how long
ivermectin treatment would need to
be continued to achieve the goal of
removing onchocerciasis as a public
health problem have not held up
Compounding problems associated with such questions, fears of drug resistance are starting to arise in a few hot spots across West Africa. A study of 2501 people in Ghana showed that the prevalence rate doubled between 2000 and 2005 despite treatment1 suggesting that some parasite populations may be developing resistance to the drug. Should such resistance arise there are other drugs available to target specific non-responders; but additional complications exist with these other drugs (for example doxycycline) due to the fact that they need more prolonged treatment regimes.
Looking at NTDs in Niger in the last issue of A Global Village Anna Phillips highlighted that ‘although treatment with drugs is excellent for morbidity control and maintaining low transmission rates of disease, it is not a sustainable means to eliminate such parasites forever.’ In some more isolated river basins, with seasonal transmission and no re-invasion of infected flies from elsewhere, it has been reported that ivermectin alone can lead to interruption of transmission2. More generally, however, and if a reduced efficacy of ivermectin were confirmed, questions should be asked about what are the best methods to achieve global elimination of onchocerciasis and its associated morbidities3?
Questions should be asked
about what are the best
methods to achieve global
elimination of onchocerciasis
and its associated morbidities?
As with the control of all infectious diseases, care must be taken to take heed of early warning signs of drug resistance. Only if researchers, funders and programme managers do not turn a blind eye to such warnings can river blindness truly become an affliction of the past.
Poppy Lamberton is a post-doctoral researcher at Imperial College London working on the effect of host and vector densities on onchocerciasis transmission in Ghana.
 Diawara L. et al. (2009). Feasibility of Onchocerciasis Elimination with Ivermectin Treatment in Endemic Foci in Africa: First Evidence from Studies in Mali and Senegal. PLoS NTDs.
 Basáñez M.-G. et al. (2009). River Blindness: a success story under threat? PLoS Medicine.