Comparing antibody responses to Onchocerca volvulus and non-parasite antigens in placebo-controlled and ivermectin-treated onchocerciasis patients

Serum antibodies to parasite-specific and non-parasite antigens were evaluated  using enzyme-linked immunosorbent assay (ELISA). Out of the 470 sera collected, 409 were from residents of an onchocerciasis hyper-endemic area, 55 non-endemic and 6 European normal sera served as control. The patients’ age, sex, skin  microfilaria densities, dermal and ocular clinical manifestations (colour of optic disc) have been well characterised. The study population had participated in a  placebocontrolled (n=191) trial of ivermectin (Mectizan®) treatment (n=218). The parasite antigens are phosphate buffered saline crude extract of adult worms of Onchocerca volvulus, a recombinant antigen (Ov1.9) and a monoclonal antibody purified antigen (Cam 1). The non-parasite antigens are deoxycholate citrate extract of optic nerve (nerve-DOC) and commercially available IgA, IgM and IgG were used to assay for rheumatoid factor (Rh-F) auto-antibodies. Generally, antibodies to parasite antigens in onchocerciasis patients were remarkably higher than control group (p<0.05) using exact F-test. There was no significant difference (p>0.05) in antibodies to nerve-DOC and Rh-F in patients compared to control. Antibodies increased with increasing skin snip microfilaria load from 0.69±0.28 with 0mf/mg (n=54) as against 0.80±0.26 for those with 4-20mf/mg. Observed slight negative correlation in IgG antibody levels and severity of disc colour with mean OD values of 0.26±0.22 in those graded as having no optic nerve disease (OND) (disc 1, n=86) and 0.17±0.19 for those with severe changes (disc 3, n=49) was not statistically significant (P>0.05). An age dependent significant decrease (P<0.05) in antibodies were observed with 0.64±0.34 for 15-30yr old (n=48) compared to 0.48±0.35 for those 50yr (n=50) for PBS with a similar trend for IgG to Ov1.9 and Cam1. In conclusion, serum parasite-specific and non-parasite antibodies may not be responsible for the pathology of optic nerve disease. Onchocerciasis patients were apparently not at higher risk of developing rheumatoid arthritis than the control.Keywords: Onchocerciasis; Antibodies; Antigens; Immune responses; Ivermectin

Red-dot card test of the paracentral field as a screening test for optic nerve disease in onchocerciasis.

A new screening test for optic nerve pathology is described, consisting of a series of four red targets presented at an angle of 12 degrees in the paracentral field above and below the horizontal meridian. Nonperception and desaturation of the targets are recorded. Inter-observer variability studies found a kappa value = 0.8. A total of 6831 individuals aged > or = 5 years in communities that were mesoendemic for savanna onchocerciasis in Kaduna State, northern Nigeria, were screened using the test. Of the participants 22% were unable to complete the test; almost two-thirds of these (62%) were aged 5-8 years. After exclusion of those visually impaired or blind according to WHO criteria and those unable to complete the test, the test showed a sensitivity of 40% and a specificity of 98% for optic nerve disease when inability to visualize one or more targets was used as the definition of test failure. The sensitivity increased to 54% with a specificity of 96% when the criterion for failure included desaturation of one or more targets. These values compare favourably with those for other available screening methods. The test took 1-2 minutes to perform and was readily accepted by patients and nurses

Impact of long-term treatment of onchocerciasis with ivermectin in Kaduna State, Nigeria: first evidence of the potential for elimination in the operational area of the African Programme for Onchocerciasis Control.

BACKGROUND: Onchocerciasis can be effectively controlled as a public health problem by annual mass drug administration of ivermectin, but it was not known if ivermectin treatment in the long term would be able to achieve elimination of onchocerciasis infection and interruption of transmission in endemic areas in Africa. A recent study in Mali and Senegal has provided the first evidence of elimination after 15-17 years of treatment. Following this finding, the African Programme for Onchocerciasis Control (APOC) has started a systematic evaluation of the long-term impact of ivermectin treatment projects and the feasibility of elimination in APOC supported countries. This paper reports the first results for two onchocerciasis foci in Kaduna, Nigeria. METHODS: In 2008, an epidemiological evaluation using skin snip parasitological diagnostic method was carried out in two onchocerciasis foci, in Birnin Gwari Local Government Area (LGA), and in the Kauru and Lere LGAs of Kaduna State, Nigeria. The survey was undertaken in 26 villages and examined 3,703 people above the age of one year. The result was compared with the baseline survey undertaken in 1987. RESULTS: The communities had received 15 to 17 years of ivermectin treatment with more than 75% reported coverage. For each surveyed community, comparable baseline data were available. Before treatment, the community prevalence of O. volvulus microfilaria in the skin ranged from 23.1% to 84.9%, with a median prevalence of 52.0%. After 15 to 17 years of treatment, the prevalence had fallen to 0% in all communities and all 3,703 examined individuals were skin snip negative. CONCLUSIONS: The results of the surveys confirm the finding in Senegal and Mali that ivermectin treatment alone can eliminate onchocerciasis infection and probably disease transmission in endemic foci in Africa. It is the first of such evidence for the APOC operational area

Impact of annual dosing with ivermectin on progression of onchocercal visual field loss.

Reported are the results of a randomized, double-masked, placebo-controlled trial of annual ivermectin dosing in 34 rural communities, Kaduna State, northern Nigeria, where guinea savanna onchocerciasis is mesoendemic. A total of 939 individuals underwent Friedmann field analysis at the first examination and saw at least 19 spots in at least one eye. Of these, 636 (68%) completed a subsequent Friedmann field analysis 2-3 years later. The adjusted incidence rate ratio for the ivermectin group versus the placebo group was 0.64 (95% confidence interval (CI): 0.42-0.98). There was some evidence that the impact of ivermectin was greatest among those who had received one dose of ivermectin. The majority of the deteriorations occurred in eyes that gave evidence of optic atrophy at the first examination. An analysis restricted to individuals with optic atrophy at baseline indicated a reduction of 45% in the incidence of visual field deterioration in the ivermectin group (95% CI: 8-67%). Previous findings have shown that ivermectin has an impact on the incidence of optic atrophy. Our results indicate, for the first time, that ivermectin has a substantial impact on the progression of visual field loss among those with pre-existing optic atrophy

An assessment of the eye care workforce in Enugu State, south-eastern Nigeria

<p>Abstract</p> <p>Background</p> <p>The availability and distribution of an appropriate eye care workforce are fundamental to reaching the goals of "VISION 2020: The right to sight", the global initiative for the elimination of avoidable blindness launched jointly by the World Health Organization and the International Agency for the Prevention of Blindness with an international membership of nongovernmental organizations, professional associations, eye care institutions and corporations. Periodic evaluation of these parameters is important in the journey towards achieving these goals. The objectives of the study were to determine the availability and distribution of human resources for eye care delivery in Enugu Urban, south-eastern Nigeria.</p> <p>Methods</p> <p>The study was designed as a cross-sectional descriptive survey, the setting for which was all public and privately owned eye care facilities in Enugu Urban, Enugu State, south-eastern Nigeria, in October 2006. The health map of Enugu Urban and the hospital register of the Public Health Department of the Enugu State Ministry of Health were used to identify the eye health care facilities in Enugu Urban. A structured, pretested, researcher-administered questionnaire was used to capture data on cadre and distribution of the eye care personnel in these facilities.</p> <p>Relevant population data were obtained from the Enugu Regional Office of the National Population Commission. Descriptive statistical analysis was used to generate percentages and proportions. Eye care personnel-to-population ratios were calculated and compared to World Health Organization recommendations.</p> <p>Results</p> <p>Out of Enugu State's population of three million, Enugu Urban accounts for 22%. The population of Enugu Urban is distributed between the three-component Local Government Areas comprising Enugu North (31%), Enugu South (30%) and Enugu East (39%). There are 45 eye care facilities (public: 31 (69%); private: 14 (31%)) employing 252 eye care workers (public: 226 (90%); private: 26 (10%)) aged 18 to 63 (mean = 36.1 years, SD = 2 years) comprising males (36: 14%) and females (216: 86%), giving a male-to-female sex ratio of 1:6. The available eye care workforce is unevenly distributed between Enugu North (128: 51%), Enugu South (65: 26%) and Enugu East (59: 23%) Local Government Areas.</p> <p>Conclusion</p> <p>Using broad and crude World Health Organization standards for minimum provider-to-population ratios, there is a sufficient eye care workforce in Enugu Urban. However, the maldistribution of the workforce creates a major barrier to uptake of eye care services. Policy modifications could reverse this maldistribution.</p

Feasibility of Onchocerciasis Elimination with Ivermectin Treatment in Endemic Foci in Africa: First Evidence from Studies in Mali and Senegal

The control of onchocerciasis, or river blindness, is based on annual or six-monthly ivermectin treatment of populations at risk. This has been effective in controlling the disease as a public health problem, but it is not known whether it can also eliminate infection and transmission to the extent that treatment can be safely stopped. Many doubt that this is feasible in Africa. A study was undertaken in three hyperendemic onchocerciasis foci in Mali and Senegal where treatment has been given for 15 to 17 years. The results showed that only few infections remained in the human population and that transmission levels were everywhere below postulated thresholds for elimination. Treatment was subsequently stopped in test areas in each focus, and follow-up evaluations did not detect any recrudescence of infection or transmission. Hence, the study has provided the first evidence that onchocerciasis elimination is feasible with ivermectin treatment in some endemic foci in Africa. Although further studies are needed to determine to what extent these findings can be extrapolated to other areas in Africa, the principle of onchocerciasis elimination with ivermectin treatment has been established

Onchocerciasis: The Pre-control Association between Prevalence of Palpable Nodules and Skin Microfilariae

*Background*: The prospect of eliminating onchocerciasis from Africa by mass treatment with ivermectin has been rejuvenated following recent successes in foci in Mali, Nigeria and Senegal. Elimination prospects depend strongly on local transmission conditions and therefore on pre-control infection levels. Pre-control infection levels in Africa have been mapped largely by means of nodule palpation of adult males, a relatively crude method for detecting infection. We investigated how informative pre-control nodule prevalence data are for estimating the pre-control prevalence of

Why are mineralocorticoid receptor antagonists cardioprotective?

Two clinical trials, the Randomized ALdosterone Evaluation Study (RALES) and the EPlerenone HEart failure and SUrvival Study (EPHESUS), have recently shown that mineralocorticoid receptor (MR) antagonists reduce mortality in patients with heart failure on top of ACE inhibition. This effect could not be attributed solely to blockade of the renal MR-mediated effects on blood pressure, and it has therefore been proposed that aldosterone, the endogenous MR agonist, also acts extrarenally, in particular in the heart. Indeed, MR are present in cardiac tissue, and possibly aldosterone synthesis occurs in the heart. This review critically addresses the following questions: (1) is aldosterone synthesized at cardiac tissue sites, (2) what agonist stimulates cardiac MR normally, and (3) what effects are mediated by aldosterone/MR in the heart that could explain the beneficial effects of MR blockade in heart failure? Conclusions are that most, if not all, of cardiac aldosterone originates in the circulation (i.e., is of adrenal origin), and that glucocorticoids, in addition to aldosterone, may serve as the endogenous agonist of cardiac MR. MR-mediated effects in the heart include effects on endothelial function, cardiac fibrosis and hypertrophy, oxidative stress, cardiac inotropy, coronary flow, and arrhythmias. Some of these effects occur via or in synergy with angiotensin II, and involve a non-MR-mediated mechanism. This raises the possibility that aldosterone synthase inhibitors might exert beneficial effects on top of MR blockade