RIVER BLINDNESS: Human onchocerciasis (river blindness) is a serious neglected tropical disease caused by the filarial nematode parasite Onchocerca ( RIVER BLINDNESS) volvulus and an important cause of blindness and chronic disability in the developing world. Presently, it is estimated that 37 million people carry O. volvulus, with 90 million at risk in Africa.
Morbidity at present is estimated at 987,000 disability-adjusted life-years and there are 46,000 new cases of blindness annually due to river blindness. Through mass drug administration of the donated drug ivermectin (Mectizan) onchocerciasis (river blindness) has been recognized by the World Health Organization as a potential candidate for global elimination, with a World Health Assembly goal to establish community based sustainable treatments of river blindness in areas of meson and hyperendemicity..
However, formidable technical and logistical obstacles must be overcome before the goal of elimination of river blindness can be attained, and additional tools are critically needed to support the control measures and thus potentially eliminate this infection as a public health problem. These new control tool requirements include a need for a vaccine against onchocerciasis (river blindness ) to “complement” the present Control measures and further the goals of the existing control programs (. The rationale for why a vaccine is in critical need includes the observations that:
(a) The present control measures are not going to succeed in the elimination of O. volvulus infection by themselves (Dadzie et al., 2003 )
(b) Evidence for emerging resistance to ivermectin, the only drug used for mass treatment of onchocerciasis (Osei-Atweneboana et al., 2007); and
(c) Practical considerations in treating people for 14 – 35 Years (Winnen et al., 2002; Boat in and Richards, 2006).Importantly, protective immunity against Onchocerca (river blindness ) Infective larval stages, also known as third-stage larvaeor L3, has now been definitively demonstrated inhumans, cattle, and mice, thereby proving the conceptualunderpinnings that a vaccine can be producedagainst this infection. The value of developing a vaccine against O. volvulus infection was recognized by the Edna McConnell Clark Foundation.
Their 15 years of support (1985–1999) provided the research foundation for antigen discovery and development of animal models for testing the efficacy of vaccine candidates. This chapter will highlight the current status of vaccine development against onchocerciasis (RIVER BLINDNESS) and the potential for being able to accelerate vaccine development to provide this crucial element required for the successful elimination of onchocerciasis.
Reduction in worm burden after vaccination, even if not absolute, will reducethe number of microfilariae produced by the adult female worms, and thereby reduce both pathology and the rates of transmission within endemic regions.
RIVER BLINDNESS IN THE TROPICS
Scabies, insect bites, hypersensitivity reactions, malaria rubra, and contact dermatitis enter the differential diagnosis of acute pruritic disease which causes river blindness. In expatriates, Calabar swellings, clinically similar episodes of localized rash and mild angioedema can mimic onchodermatitis. Tuberculoid leprosy and eczema should be considered if there are chronic skin changes. Dermatomycoses, previous trauma, and yaws can also cause hypopigmented skin lesions.
The differential diagnosis of onchocercomas (river blindness) comprises lipomas, fibromas,lymph nodes, cysticerci, dermoid cysts,foreign body granulomas, exostosis, and ganglia. Onchocercal chorioretinitis (RIVER BLINDNESS) must be differentiated from choroiditis due to syphilis,tuberculosis, or toxoplasmosis. Optic neuropathy in endemic areas may be due to nutritional optic atrophy, syphilis, or primary glaucoma. In expatriates with a suggestive history (i.e. being a travel partner of a skin snip positive patient) but with negative skin snips and no nodules, presumptive diagnosis can be made by Mazzotti test and/ or serology.
TREATMENT AND PROGNOSIS OF RIVER BLINDNESS
Because the pathologic sequelae of O.volvulus infection are due to microfilariae in skin and ocular tissues, a treatment leading to sustained absence of microfilariae is necessary for morbidity reduction. This can be achieved either by repeated treatment with drugs active against microfilariae for the lifetime of adult worms (up to 14 years), or by killing or removing the adult worms. In principle there are two modes of treatment available for onchocerciasis (river blindness) : nodulectom, and microfilaricidal or macrofilaricidaldrugs.
Ivermectin (Campbell, 1991) elicits receptor-mediated hyperpolarization of cells after an influx of negatively charged ions occurs utilizing a novel glutamate sensitive chloride channel presentin nematodes. Ivermectin is well absorbed oral, excretion is almost entirely in the feces, and its serum half-life is 12 hours. Large field trials in Africa in the 1980s established ivermectin as the treatment of choice in a single oral microfilaricidal dose of 150 µ g/kg administered every 6–12 months. Skin microfilariae are decreased within days though maximum reduction may not occur for up to 2 weeks. Because drug effects are so much longer than its half-life, and because histologically, immune effector cells attack the damaged microfilariae microfilariae for identification.In contrast to M. streptocerca,
O.volvulus microfilariae are longer and thicker (55–9 µ m in contrast to 3–5 µ m width and a maximum length of 260 µ m for M. streptocerca ),have anterior nuclei that are side by side, a caudal space free of nuclei, and a tail tapered to a fine point. M. streptocerca is most often found in snips taken from the upper trunk.
This drug, currently in phase II efficacy studies, is structurally similar to ivermectin and has shown more sustained diminution of microfilariae in animal models. The hope is therefore that moxidectin may reduce microfilarial loads and thus transmission better than does ivermectin. Since the drug has the same mode of action and binds to the same sites, it is uncertain whether it could act as a replacement for ivermectin were ivermectin resistance to spread.
TREATMENT AND PROGNOSIS OF RIVER BLINDNESS