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PubMed1989

The chemotherapy of onchocerciasis. XIII. Studies with ivermectin in onchocerciasis patients in northern Ghana, a region with long lasting vector control.

One hundred and ninety eight patients with moderate to heavy infections with Onchocerca volvulus were randomly assigned to receive single doses of 100, 150 or 200 mcg/kg of ivermectin or matching placebo capsules. Detailed systemic, ocular and parasitological examinations were carried out at intervals over a period of one year. Nodules were excised twelve months after treatment to evaluate the effect of the treatment with ivermectin in adult O. volvulus. The three ivermectin-treated groups produced massive reductions in skin microfilariae (over 97%) with low levels being maintained over one year. The 150 and 200 mcg/kg doses were however superior to the 100 mcg/kg dose in achieving a greater reduction in skin microfilarial counts initially and in maintaining significant lower levels throughout the period of observation. There was no difference between the 150 and 200 mcg/kg doses at anytime. The three ivermectin doses were equally effective in the clearance of ocular microfilariae. The proportion of dead adult worms was very high in all treatment groups, which is effected by the successful ten years lasting vector control in northern Ghana. In spite of this superannuation of the worm population, an impact of the treatment with ivermectin on the reproductivity of the parasite could be shown. Systemic total clinical reaction was mild and was similar in the ivermectin treated groups. However, severe symptomatic postural hypotension (SSPH) was limited to patients treated with 150 or 200 mcg/kg of ivermectin. Ocular reactions were mild in all patients and no ocular deficiency occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2003

Final report of the Conference on the eradicability of Onchocerciasis.

Sixty-four experts from a variety of disciplines attended a Conference on the Eradicability of Onchocerciasis at The Carter Center, in Atlanta GA, held January 22-24, 2002. The Conference, which was organized by The Carter Center and the World Health Organization, with funding from the Bill & Melinda Gates Foundation, addressed the question: "Is onchocerciasis (River Blindness) eradicable with current knowledge and tools?" Former US President Jimmy Carter attended part of the final plenary proceedings on January 24.The Conference consisted of a series of presentations by invited expert speakers (Appendix C) and further deliberations in four workgroups (Appendix D) followed by plenary discussion of major conclusions. The presentations underlined epidemiological and entomological differences between onchocerciasis in Africa and the Americas. Whilst onchocerciasis in Africa covers extensive areas and is associated with striking human and fly population migrations and remarkably efficient black fly vectors, in the Americas onchocerciasis is found in limited foci. Human and fly population migration are not major problems in the Americas, where most black fly species are inefficient, though some efficient black flies are also found there. Vector control has been effectively applied in the Onchocerciasis Control Program in West Africa (OCP) with remarkable results, interrupting transmission in most parts of the original Program area. The use of ivermectin has given variable results: while ivermectin treatment has been effective in all endemic areas in controlling onchocerciasis as a public health problem, its potential for interrupting transmission is more promising in hypo- and mesoendemic areas. The African Program for Onchocerciasis Control (APOC), which supports onchocerciasis control in endemic African countries outside the OCP, applies ivermectin, its principal control tool, to communities in high-risk areas as determined by rapid epidemiological mapping of onchocerciasis (REMO) and Geographic Information Systems (GIS). In the Americas, through support of the Onchocerciasis Elimination Program in the Americas (OEPA), a strategy of bi-annual ivermectin treatment of at least 85% of the eligible populations in all endemic communities is showing very good results and promises to be effective in eliminating onchocerciasis in the region.The Conference concluded that onchocerciasis is not eradicable using current tools due to the major barriers to eradication in Africa. However, the Conference also concluded that in most if not all the Americas, and possibly Yemen and some sites in Africa, transmission of onchocerciasis can be eliminated using current tools. The Conference recommended that where interruption of transmission is feasible and cost effective, programs should aim for that goal using all appropriate and available interventions so that the Onchocerca volvulus can eventually be eliminated and interventions halted. Although interruption of transmission of onchocerciasis cannot currently be achieved in most of Africa, the Conference recommended that efforts be made to preserve areas in West Africa made free of onchocerciasis transmission through the Onchocerciasis Control Program over the past 25 years. In the remaining hyper and mesoendemic foci in Africa, continued annual distribution of ivermectin will keep onchocerciasis controlled to a point where it is no longer a public health problem or constraint to economic development.

Journal Article↗
PubMed1994

Major retinal cell components recognized by onchocerciasis sera are associated with the cell surface and nucleoli.

PURPOSE: Cellular localization of the components recognized by onchocerciasis autoantibodies has not been investigated in any detail in cultured retinal cells. This study sought to examine, in cultured retinal cells, the subcellular localization of major components that cross-react with onchocerciasis sera. METHODS: Immunofluorescence confocal laser scanning microscopy and Western blot analysis were carried out on adult pig retinal cells. RESULTS: The onchocerciasis sera contain antibodies cross-reacting strongly with components of the surface and nucleoli in both the cultured retinal pigment epithelial and neural retinal cells. These epitopes are not recognized by the control sera obtained from noninfected individuals residing in an onchocerciasis hyperendemic area, and from those with or without ocular disease who have never been in any of the onchocerciasis hyperendemic countries. Double-labeling immunofluorescence microscopy does not detect any colocalization of a putative onchocerciasis autoantigen, calreticulin, and those cellular components recognized by onchocerciasis sera in either cell type. Furthermore, none of the onchocerciasis sera tested recognized recombinant calreticulin by Western blot analysis. CONCLUSIONS: Major epitopes for onchocerciasis anti-retinal autoantibodies are associated with the surface and nucleolus components of retinal cells. Interaction of the onchocerciasis antibodies with the retinal cell surface molecules may play an important role in the development of ocular diseases initiated by the damage of retinal cells. Furthermore, the finding that the cellular components recognized by onchocerciasis sera do not colocalize with calreticulin, taken together with the observation of lack of recognition of recombinant calreticulin by these sera on Western blots, suggests that calreticulin is not a major onchocerciasis autoantigen.

Animals↗
PubMed1990

Humoral and cell-mediated immune response against human retinal antigens in relation to ocular onchocerciasis.

Autoimmune mechanisms are thought to be involved in the pathogenesis of the chorioretinal changes in ocular onchocerciasis. The humoral autoimmune response was determined by measuring serum levels of autoantibodies, directed against human S-antigen and interphotoreceptor retinoid binding protein (IRBP) using an enzyme immunoassay. The cell-mediated immune response to these antigens and a crude retinal extract was investigated by means of a two-step migration inhibition factor assay. Patients with onchocerciasis (n = 50) were subdivided into three groups: 1. without ocular involvement (n = 10), 2. with ocular onchocerciasis limited to the anterior segment (n = 19), 3. with onchocercal chorioretinopathy (n = 21). A group of endemic controls from Sierra Leone, West Africa were also studied. The cellular immune response to Concanavalin A was measured to assess the general capacity of lymphocytes to respond to a mitogen. High levels of anti-human S-antigen and IRBP antibodies were detected in patients with onchocerciasis and endemic controls. The levels of both anti-human S-antigen and IRBP antibodies were significantly higher in onchocerciasis patients compared to endemic controls (Mann-Whitney ranksum test; p less than 0.001 respectively 0.002). No relationship could be demonstrated between the anti-retinal antibody level and the occurrence of chorioretinitis in ocular onchocerciasis. The occurrence of the anti-retinal antibodies as a result of crossreactivity of anti-retinal antibodies with parasitic antigens or of induction of polyclonal B-cell activation due to parasitic infection is discussed, since high antibody levels were also found in patients with Bancroftian filariasis from Papua New Guinea and Surinam. The migration inhibition factor assay, in which the cell-mediated immune response to human S-antigen, IRBP and retinal extract was tested, showed that four out of 50 (8%) patients with onchocerciasis and four out of 25 (16%) endemic controls reacted with at least one retinal antigen. From the patients with onchocercal chorioretinopathy two out of 21 (10%) showed a positive cellular response. The general mitogen response tested with Con A was positive in all these individuals. In conclusion, circulating antibodies against human S-antigen or human IRBP are thus nor specific for onchocerciasis and in themselves not sufficient to cause chorioretinopathy in onchocerciasis, although their pathogenic role in an ongoing chorioretinitis cannot be excluded. Furthermore a role for a cell-mediated anti-retinal autoimmune mechanism in the pathogenesis of chorioretinitis in onchocerciasis as studied with human S-antigen, IRBP or crude retinal extract could not be demonstrated.

Antigens↗
PubMed2005

Onchocerciasis: a potential risk factor for glaucoma.

BACKGROUND: Onchocerciasis is a microfilarial disease that causes ocular disease and blindness. Previous evidence of an association between onchocerciasis and glaucoma has been mixed. This study aims to further investigate the association between onchocerciasis and glaucoma. METHODS: All subjects were patients at the Bishop John Ackon Christian Eye Centre in Ghana, west Africa, undergoing either trabeculectomy for advanced glaucoma or extracapsular extraction for cataracts, who also had a skin snip biopsy for onchocerciasis. A cross sectional case-control study was performed to assess the difference in onchocerciasis prevalence between the two study groups. RESULTS: The prevalence of onchocerciasis was 10.6% in those with glaucoma compared with 2.6% in those with cataracts (OR, 4.45 (95% CI 1.48 to 13.43)). The mean age in the glaucoma group was significantly younger than in the cataract group (59 and 65, respectively). The groups were not significantly different with respect to sex or region of residence. In models adjusted for age, region, and sex, subjects with glaucoma had over three times the odds of testing positive for onchocerciasis (OR, 3.50 (95% CI 1.10 to 11.18)). CONCLUSIONS: This study has shown a positive association between subclinical onchocerciasis and glaucoma. This finding emphasises the importance of eradication of onchocerciasis from west Africa.

Age Distribution↗
PubMed1975

Visual impairment and incidence of blindness in Liberia and their relation to onchocerciasis.

The results of the epidemiological survey of 10,860 inhabitants of 121 Liberian communities from 1969-1971 were analysed on the prevalence, incidence and risk of blindness associated with onchocerciasis infection. The overall prevalence of economic blindness in the population sample was 3.24%, the total rate of measured visual damage in both eyes was 5.37% (impairment of vision etc.). Onchocerciasis was prevalent in a very high proportion of those having visual defects. Causes of blindness as by frequency were cataract in 45%, lesions of the anterior segment, other than onchocerciasis-related in 14%, phthisis bulbi (9%) and optic atrophy (6%). The importance of onchocerciasis as a cause of blindness and as a public health problem in Liberia is examined by the comparison of 5 categories of village populations, classified by their adjusted onchocerciasis prevalence rates. The risk of exposure to onchocerciasis increases gradually from nil to 100%, providing one infection-free control population and increasing degrees of prevalence in the next categories, dependent on duration of exposure and intensity of transmission. The attempt to estimate the risk of blindness attributable to onchocerciasis from this data reveals a 3-fold risk in people exposed to the infection in their habitat, whereas a 2,5-fold risk is found from the evaluation of findings in people classified by mf-prevalence in their skins only. Considering a proportion of at least 65% of the rural population to be living under onchocerciasis exposure, the attributable risk amounts to more than 50%, which suggests that this population suffers from 50% more blindness than would be expected without exposure to onchocerciasis sometime in life.

Adolescent↗
PubMed2005

Combined Utilisation of Rapid Assessment Procedures for Loiasis (RAPLOA) and Onchocerciasis (REA) in Rain forest Villages of Cameroon.

BACKGROUND: Individuals with high microfilarial loads of Loa loa are at increased risk of neurologic serious adverse (SAE) events following ivermectin treatment against onchocerciasis. RAPLOA (Rapid Assessment Procedure for loiasis), a newly developed rapid assessment procedure for loiasis that relates the prevalence of key clinical manifestation of loiasis (history of eye worm) to the level of endemicity of the infection (prevalence of high intensity), is a very useful tool to identify areas at potential risk of L. loa post ivermectin treatment encephalopathy. In a perspective of treatment decision making in areas of co-endemicity of loiasis/onchocerciasis, it would be advantageous (both in time and cost savings) for national onchocerciasis control programmes to use RAPLOA and the Rapid epidemiologic assessment for onchocerciasis (REA), in combination in given surveys. Since each of the two rapid assessment tools have their own specificities, the workability of combining the two methods needed to be tested. METHODS: We worked in 10 communities of a forest area presumed co-endemic for loiasis and onchocerciasis in the North-West Province of Cameroon where the mass-treatment with ivermectin had not been carried out. A four-step approach was used and comprised: (i) generating data on the prevalence and intensity of loiasis and onchocerciasis in an area where such information is scarce; (ii) testing the relationship between the L. loa microfilaraemia prevalence and the RAPLOA prevalence, (iii) testing the relationship between the O. volvulus microfiladermia prevalence and the REA prevalence, (iv) testing the workability of combining RAPLOA/REA by study teams in which a single individual can perform the interview for RAPLOA and the nodule palpation for REA. RESULTS: The microfilaraemia prevalence of loiasis in communities ranged from 3.6% to 14.3%. 6 (0.61%) individuals had L. loa microfilarial loads above 8000 mf/ml but none of them attained 30,000 mf/ml, the threshold value above which the risk of developing neurologic SAE after ivermectin treatment is very high. None of the communities surveyed had RAPLOA prevalence above 40%. All the communities had microfiladermia prevalence above 60%. The microfiladermia results could be confirmed by the rapid epidemiologic method (nodule palpation), with all the 10 communities having REA prevalence above 20%. For the first time, this study has demonstrated that the two rapid assessment procedures for loiasis and onchocerciasis can be carried out simultaneously by a survey team, in which a single individual can administer the questionnaire for RAPLOA and perform the nodule palpation for REA. CONCLUSION: This study has: (i) Revealed that the Momo valley of the North West province of Cameroon is hyperendemic for onchocerciasis, but is of lower level of endemicity for L. loa. (ii) Confirmed the previous relationships established between RAPLOA and the L. loa microfilaraemia prevalence in one hand and between the REA and the O. volvulus microfiladermia prevalence in another hand (iii) Shown that RAPLOA and REA could be used simultaneously for the evaluation of loiasis and onchocerciasis endemicity in areas targeted by the African Programme for onchocerciasis Control for community-directed treatment with ivermectin (CDTI).

Journal Article↗
PubMed1997

[Human onchocerciasis in Africa].

Before the 1980s, the only available method for control of onchocerciasis was elimination of blackfly vector populations. This strategy was used with considerable success in the Onchocerciasis Control Programme in West Africa (OCP). The discovery of ivermectin, the first effective drug suitable for mass treatment of onchocerciasis, has revived international interest not only in fundamental research but also in development of new strategies to control onchocerciasis in the countries outside the OCP area. This report gives an overview of current parasitological, clinical, epidemiological and diagnostic data about onchocerciasis. Although little is known about the early development of Onchocerca volvulus in the human host, significant insight has been gained into the population dynamics of the parasite. The pathogenesis of cutaneous and ocular manifestations in onchocerciasis is now better understood. Epidemiological studies are under way to evaluate the extent of systemic manifestations. Recently developed diagnostic methods are more sensitive than conventional parasitological techniques. A new method for rapid assessment of endemic level has provided a detailed picture of the distribution of onchocerciasis. Species- and strain-specific DNA probes have been developed for identification of parasites in West Africa. New methods for quantifying disability allow evaluation of the socio-economic impact of the cutaneous and ocular complications of onchocerciasis.

Africa↗
PubMed1996

Ivermectin-induced immunopotentiation in onchocerciasis: recognition of selected antigens following a single dose of ivermectin.

Onchocerciasis is associated with blindness and gross skin changes, believed to be a consequence of the immune response to antigens released from the offspring of the female worm of Onchocerca volvulus, the microfilariae (mf). An effective microfilaricidal drug is now available which quickly reduces the mf burden without affecting the adult worm. There exist foci in onchocerciasis endemic areas where some of the patients have many mf in their skin but relatively few clinical symptoms. This state of hyposensitivity is believed to be due to immunosuppression. The aim of this study was to address the question of the basis of, and the effect of ivermectin treatment on this immunosuppression. Female adult worms of O. volvulus were used as whole or fractionated antigens to stimulate peripheral blood mononuclear cells. Microfilariae are found in the reproduction tract of the female worms, and thus an antigen preparation of the female adult O. volvulus contains both exclusive adult antigens as well as antigens from microfilariae. Cells were obtained from onchocerciasis patients, individuals of similar socio-economic status living in the same Ghanaian village, but who showed no parasitological or clinical evidence of onchocerciasis (exposed endemic controls), healthy Ghanaians living in areas where transmission of onchocerciasis does not seem to occur (non-exposed endemic controls) and unexposed healthy Swedish donors. As a group, cells from onchocerciasis patients proliferated to a lesser degree than cells from the exposed endemic control and the non-exposed endemic control groups to the whole worm antigen, whereas the phytohaemagglutinin (PHA) response was strongest in the patients. Proliferative responses of above 1000 ct/min to fractions of the worm extract were only evident in the cells from a few individuals in each of the various groups. However, 28 days following ivermectin treatment, cells from all onchocerciasis patients were able to mount significantly enhanced proliferation to a fraction of approximately 96 kD (fraction 3), while only four of nine of this group showed an increased response to the whole worm antigen. The proportional increase in the response to the whole organism in these individuals was of a much lower magnitude than the increased response to fraction 3. The O. volvulus antigen-specific immunosuppression observed in these onchocerciasis patients appears to be due to suppressive antigens which have the capacity to mask the potential response to selected antigens of O. volvulus, and ivermectin treatment possibly modulates the immune response, allowing for stepwise recognition of such antigens. Since ivermectin treatment kills only the microfilariae and not the adult worm, the putative suppressive antigens would be expected to be from the microfilariae.

Adolescent↗
PubMed1999

The causes and profile of visual loss in an onchocerciasis-endemic forest-savanna zone in Nigeria.

In an onchocerciasis-endemic forest-savanna mosaic zone of southeastern Nigeria, blindness was found in 5.4% of 1,217 people who voluntarily attended for examination from a population of 14,000. Apart from cataract, the most important causes of blindness in the area were eye diseases that are known to be associated with onchocerciasis. Refractive error, although a non-onchocerciasis-related eye defect, was the number one cause of visual loss found in the study. The causes of blindness in our examined population are similar to what is found in onchocerciasis-endemic areas of the savanna zone and dissimilar from those found in the forest zone. In this forest-savanna mosaic zone, the prevalence of onchocerciasis was higher in the respondents with poor vision than in those with adequate vision. Similarly, low vision was found to be more common in people with high microfilarial loads, but people with high loads also tended to be older than those with moderate or low microfilarial loads, which might suggest that low vision was only a function of age. Nonetheless, analysis of our data shows evidence of an association between low vision and microfilarial load in adults aged 60 years and above. It is concluded that onchocerciasis in the forest-savanna mosaic zone of Nigeria has the features until recently associated only with savanna onchocerciasis, and that this should be taken into consideration in planning and executing onchocerciasis control programs in the area.

Adolescent↗