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PubMed2001

Macrofilaricides and onchocerciasis control, mathematical modelling of the prospects for elimination.

BACKGROUND: In most endemic parts of the world, onchocerciasis (river blindness) control relies, or will soon rely, exclusively on mass treatment with the microfilaricide ivermectin. Worldwide eradication of the parasite by means of this drug is unlikely. Macrofilaricidal drugs are currently being developed for human use. METHODS: We used ONCHOSIM, a microsimulation mathematical model of the dynamics of onchocerciasis transmission, to explore the potentials of a hypothetical macrofilaricidal drug for the elimination of onchocerciasis under different epidemiological conditions, as characterized by previous intervention strategies, vectorial capacity and levels of coverage. RESULTS: With a high vector biting rate and poor coverage, a very effective macrofilaricide would appear to have a substantially higher potential for achieving elimination of the parasite than does ivermectin. CONCLUSIONS: Macrofilaricides have a substantially higher potential for achieving onchocerciasis elimination than ivermectin, but high coverage levels are still key. When these drugs become available, onchocerciasis elimination strategies should be reconsidered. In view of the impact of control efforts preceding the introduction of macrofilaricides on the success of elimination, it is important to sustain current control efforts.

Animals↗
PubMed1983

Sowda--onchocerciasis in north Yemen: a clinicopathologic study of 18 patients.

Sowda is an unusual form of onchocerciasis in Yemenites that differs from African onchocerciasis. Clinical and pathological studies were performed on 18 patients in Yemen Arab Republic (North Yemen). Biopsies of skin and lymph nodes were taken, and then processed at the Armed Forces Institute of Pathology, Washington, D.C. The most striking clinical features were swollen, darkened, pruritic, papular skin changes that were usually limited to one leg, more rarely to one arm, and large soft regional lymph nodes. Dermal changes were deeper and more diffuse than in African onchocerciasis, with many large fibroblasts and plasma cells. Microfilariae of Onchocerca volvulus were much rarer in skin from Yemenites with sowda. When patients were treated with diethylcarbamazine, the dermatitis became suddenly worse as the microfilariae degenerated and provoked acute inflammation. The dermatitis decreased after several days of treatment. Enlarged lymph nodes from sowda have shown follicular hyperplasia, in contrast to follicular atrophy and perivascular fibrosis that are characteristic of lymph nodes from cases of African onchocerciasis. Cell-mediated and humoral immunity may be more active in sowda than in African onchocerciasis.

Adolescent↗
PubMed1999

Analysis of renal function in onchocerciasis patients before and after therapy.

The occurrence of renal abnormalities was investigated in patients with onchocerciasis in comparison to individuals without onchocerciasis in Guinea. Serum creatinine levels, excretion of urinary marker proteins, and kidney size by ultrasound were determined. A high prevalence of glomerular as well as tubular dysfunctions was observed; however, no association with onchocerciasis could be detected. We also hypothesized that patients with hyperreactive onchocerciasis might be prone to develop immune-mediated glomerular disorders; however, this could not be verified. Following treatment with ivermectin, a slight but significant increase in the excretion of urinary albumin and alpha1-microglobulin was seen five days after treatment in all treated patients, whereas levels of proteinuria were significantly higher five days after treatment only in patients with high microfilarial densities. Our results indicate that ivermectin can cause glomerular and tubular disturbances in patients with onchocerciasis; however, these are minor and do not seem to be clinically relevant.

Adult↗
PubMed2002

Lymphatic filariasis elimination and schistosomiasis control in combination with onchocerciasis control in Nigeria.

This paper describes a pilot initiative to incorporate lymphatic filariasis (LF) elimination and urinary schistosomiasis (SH) control into a mature onchocerciasis control program based on community-directed ivermectin treatment in central Nigeria. In the same districts having onchocerciasis we found LF (as determined by blood antigen testing in adult males) in 90% of 149 villages with a mean prevalence of 22.4% (range 0-67%). Similarly, SH, as determined by dipstick reagent testing for blood in urine from school children, was found in 91% of 176 villages with a mean orevalence in school age children of 24.4% (range 0-87%). Health education and treatment interventions for SH resulted in 52,480 cumulative praziquantel treatments, and 159,555 combined onchocerciasis and LF treatments (with ivermectin and albendazole) as of the end of 2000. Treatments for onchocerciasis and LF were separated by at least 1 week from treatments for SH. There was no negative impact on the coverage of the onchocerciasis program by the addition of LF and SH activities.

Anthelmintics↗
PubMed1999

Rapid epidemiological mapping of onchocerciasis in areas of Uganda where Simulium neavei sl is the vector.

OBJECTIVE: To test whether Rapid Epidemiological Mapping of Onchocerciasis (REMO) was suitable for mapping of onchocerciasis in foci where S. neavei sl is the primary vector. DESIGN: Topographical maps of scale 1:250,000 were used in demarcating regions into ecotopographic divisions and zones in order to identify potential onchocerciasis endemic areas. SETTING: The study was conducted in Kabarole and Nebbi districts. High-risk communities were selected 30 km from each other, and closest to rivers where vector breeding appeared likely. Secondary and additional communities were selected 10 km and 20 km away from high-risk communities, respectively. SUBJECTS OR PARTICIPANTS: Communities were mobilised for nodule palpation. A sample of thirty males aged at least 20 years, from each community that had lived in the area for at least ten years, were randomly selected and examined. INTERVENTIONS: Individuals positive for at least one nodule were expressed in terms of Nodule Prevalence Rates (NPR) which were used to map the distribution of onchocerciasis. MAIN OUTCOME MEASURES: Coefficient of variation (CV) of Nodule Prevalence Rates between high risk secondary communities. RESULTS: In Kabarole district, the results indicated a low coefficient of variation (CV) of 75 in NPR between high risk and secondary communities while in Nebbi district, higher CV of 187.4 was attained. The less varied NPR implies that communities in Kabarole were almost equally exposed to onchocerciasis while highly varied situation in Nebbi indicated decreasing NPR with increasing distance from high-risk communities. CONCLUSION: REMO is applicable in areas where S. neavei sl is the primary vector, for identification and mapping communities requiring mass treatment with ivermectin.

Adult↗
PubMed2001

[Human onchocerciasis and "sowda" in the Republic of Yemen].

The geophysics of the north Yemen, associating a north-south directed mountainous fish bone (rising in more of 2,000 meters), to numerous rivers or "wadis" is convenient to the development of simulium shelters, main vectors for cutaneous filariasis to Onchocerca sp. Following several missions of bio-clinical and epidemiological evaluations in neighbouring villages of wadis, it has been possible to study different clinical aspects: one reminding the classical african onchocerciasis with generalized and diffused dermatitis, and, on an other hand, a hyperreactive dermatitis on one side of the body and associated with a collateral lymphatic ganglion. This disease is well known for local populations as "aswad" meaning "black" or "sowda". Clinically whatever the studied focus, coexists the two types of onchodermatitis (uni or bilateral). Yhe sowda patients are proportionally less numerous than those touched by the generalized type. Frequent eye lesions of the West African onchocerciasis are not found in sowda cases. In classical optical microscopy, microfilaria is morphologically indifferenciable between sowda and onchocerciasis clinical aspects. Skin snips were carried out on patients of both groups. Identification of microfilaria by molecular biology through the study of the DNA genome was done out of 5 skin snips. Microfilaria was kept dry between laminas and the DNA extracted from rehydrated microfilaria. DNA was intensified with specific primers of Onchocerca type (O150PCR). This phase was followed by hybridisation of amplification products by PCR to specific stains: OVS-2 for Onchocerca volvulus species, OCH for Onchocerca ochengi, PFS1 and PSS1-BT respectively for the forest strain and the savannah strain of Onchocerca volvulus as described previously. We can distinguish 2 kinds of answers based on the clinical origin of the snip-tests: the first one concern 3 patients with numerous dermal microfilariae but without any clinical sowda and corresponding to microfilaria O. volvulus type but different from the forest or savannah strains found in sub-Saharan Africa. The second one corresponds to 2 patients with less than 5 microfilaria in their snip-test. They show the typical clinical picture of sowda. They are identified as microfilaria type Onchocerca but they do not belong to species volvulus, or to species ochengi. It seems quite probable that the clinical picture of sowda be the result of developing onchocerciasis of animal origin and not identified as to day. The ivermectin, therapeutic of choice for African onchocerciasis in annual unique cure seems less effective in the coverage of sowda. In that case rehearsal of cures every 3 months would be necessary for mass campaigns to limit the transmission of this filariasis.

Animals↗
PubMed2003

Onchocerciasis among Ethiopian immigrants in Israel.

BACKGROUND: Onchocerciasis results from infestation by the nematode Onchocerca volvulus, and is characterized clinically by troublesome itching, skin lesions and eye manifestations. Since 1992, approximately 9,000 immigrants have arrived in Israel from the Kuwara province of northwest Ethiopia where the prevalence of onchocerciasis is particularly high. OBJECTIVES: To determine whether onchocerciasis is the cause of cutaneous and ocular symptoms among recent immigrants from the Kuwara province in Ethiopia. METHODS: We examined 1,200 recent immigrants from the Kuwara province residing at the Mevasseret Zion immigration center outside Jerusalem. Among them, patients with cutaneous signs suggestive of onchocerciasis underwent a skin-snip biopsy and a thorough eye examination. RESULTS: In the detailed skin examination performed in 83 patients, the most common skin finding was chronic papular onchodermatitis, found in more than 46 patients (55%); depigmentation and atrophy was found in 13 (15%) and 12 (14%), respectively. In 40 patients (48%), living microfilaria were detected in their skin snips. Of the 65 patients who underwent a through eye examination, 45 patients (66%) had ocular complaints. Corneal abnormalities were found in 55 of the 130 eyes (42%), active anterior segment intraocular inflammation and live microfilariae were found in 4 eyes (3%) and lens changes in 16 eyes (1%). Eleven eyes (9%) showed retinal or choroidal changes. CONCLUSIONS: Skin and eye manifestations associated with onchocerciasis are prevalent among symptomatic Ethiopians who immigrated to Israel from the Kuwara province.

Adolescent↗
PubMed1992

Ocular onchocerciasis and the intensity of infection in the community. IV. The degraded forest of Sierra Leone.

To assess the pattern of onchocercal ocular disease and blindness in south Sierra Leone, ophthalmological surveys were carried out in 13 highly infected villages located in various river basins. The most important finding was the blinding potential of onchocerciasis in the degraded forest area where the prevalence of onchocercal blindness reached levels of up to 6%. This is remarkable since previous studies have claimed onchocerciasis in the forest to cause little blindness. Ocular onchocerciasis undoubtedly constitutes a problem of public health importance in south Sierra Leone. The rates of onchocercal ocular disease and blindness, however, were significantly lower than those found in savanna villages with similar levels of endemicity. The community pattern of ocular onchocerciasis was not significantly different from the classical pattern in the forest but this could be explained by the low endemicity levels in the forest villages studied. It is therefore not possible to deduce from this study whether the pattern of ocular onchocerciasis in south Sierra Leone is of the forest type, or a pattern on its own.

Adolescent↗
PubMedDate not supplied

[Changes in the peripheral leukocytes of onchocerciasis patients treated with consecutive doses of ivermectin].

The purpose of this investigation, which utilized a single-blind study with placebo, was to evaluate the peripheral leukocyte count in onchocerciasis patients treated with ivermectin. Eighty-three male patients between the ages of 12 and 60, all with moderate or severe onchocerciasis infections (but otherwise in general good health), were selected from three villages from the southern onchocerciasis endemic area of Chiapas, Mexico. All onchocerciasis patients were randomly assigned to either the ivermectin group or a placebo group in a three to one ratio, respectively. Sixty-two patients from the ivermectin group received five single oral doses of ivermectin between 150 and 220 mcg/kg (one every six months), and placebo pills of identical appearance were given to 21 patients from the placebo group. Physical, ophthalmological, and laboratory exams were performed on all patients in this study. Skin and ocular microfilaria were stimulated in all patients. Results have indicated that ivermectin induced a decrease in the total number of peripheral leukocytes to the extent of about 300 to 500 cells after each drug intake. In the majority of the cases, the reduction was due to a decrease in the total number of eosinophils; the number of neutrophils, lymphocytes, and monocytes remained at the same level after treatment. These results strongly suggest that the eosinophilia observed in the prestudy of those individuals with onchocerciasis could have induced leukocytosis (the eosinophilia decreasing significantly after administering ivermectin).

Adolescent↗
PubMed1989

Immunopathology of ocular onchocerciasis. I. Inflammatory cells infiltrating the anterior segment.

Ocular tissue (conjunctiva and iris) was obtained from 12 adult African men with active ocular onchocerciasis and from nine age-matched persons from the same endemic region but without onchocercal infection. These tissues were examined immunohistologically and two major findings were noted. First, mild-to-moderate chronic inflammatory cellular infiltration was present in the conjunctiva of the onchocerciasis patients. T lymphocytes (CD3+) were the major inflammatory cells, and the T suppressor/cytotoxic (CD8+) subset was significantly increased in the ocular onchocerciasis patients (P less than 0.03). Second, in the onchocerciasis patients, non-lymphoid cells of the conjunctiva and iris, such as vascular endothelium, pericytes and fibroblasts were in an activated state, as shown by increased expression of Class II MHC antigens (P less than 0.02, conjunctiva; P less than 0.05, iris). These concomitant findings of lymphocyte infiltration and resident cell activation indicate a dynamic state of localized host responsiveness presumably to the microfilarial parasites and their products in the anterior segments of the eyes of patients with ocular onchocerciasis.

Aged↗
PubMed1986

The status of human onchocerciasis in the Kainji reservoir basin areas 20 years after the impoundment of the lake.

A study was made in January 1985 to assess the post-impoundment status of onchocerciasis around the man-made Lake of Kainji, Nigeria, about 20 years after the formation of the lake. The overall prevalence of the infection in the 13 major villages surveyed was 28.5%. The endemicity of onchocerciasis was sporadic (less than 10%) in three of these villages, low (10-39%) in six and medium (40-69%) in four. Although the available pre-impoundment data is inadequate to make a definite conclusion of the impact of the lake formation on the status of onchocerciasis in the area, it is apparent that here, as in most other parts of the country, the prevalence, manifestations, complications and public health significance of onchocerciasis justify the ongoing campaign for the urgent implementation of a nation-wide onchocerciasis control programme in Nigeria.

Adolescent↗
PubMed1982

Detection of IgE antibodies in onchocerciasis. Possibility of using allergens from Dipetalonema viteae extracts that cross-react with allergenic determinants in crude extracts of Onchocerca volvulus.

The present study reports the presence of Onchocerca volvulus specific IgE in the sera obtained from onchocerciasis patients. About 70% of onchocerciasis patients showed a raised level of O. volvulus specific IgE compared to patients infected either with other human filarids (Loa loa, Wuchereria bancrofti, Brugia malayi) or with other helminths (Schistosoma mansoni, Ascaris lumbricoides, Fasciola hepatica). The O. volvulus specific IgE level was significantly higher in patients exhibiting 'gale filarienne' than in microfilaremic patients or in endemic controls. The total IgE level was significantly raised in the serum samples of all groups of subjects from endemic areas compared to European controls. There was no significant increase in the level of IgE in the onchocerciasis sera when O. volvulus antigen was replaced by the antigens from various helminths in the present assay system (radioallergosorbent test). However, there was a clear evidence of the presence of cross-reacting allergens in the crude extracts from adults of O. volvulus and Dipetalonema viteae (a rodent filarial parasite) because there was a significant reduction in IgE level in onchocerciasis sera following absorption with either O. volvulus or D. viteae sorbents. Moreover, the IgE antibodies in onchocerciasis patients sera recognized the allergens which were present in the somatic extracts of O. volvulus and D. viteae as revealed by radiolabelled anti-IgE.

Allergens↗
PubMed1984

The evolution of ocular onchocerciasis in the Volta River Basin Area over a period of five years of vector control.

The results of an ophthalmological evaluation conducted in seven West African savannah villages before and after 5 years of vector control, were analysed to determine the effect of an interrupted or greatly reduced transmission of Onchocerca volvulus on the evolution of ocular onchocerciasis. Cross-sectional data showed a significant reduction of the prevalence of ocular onchocerciasis in five of the villages, and the rates of irreversible ocular lesions and blindness were generally lower after 5 years of vector control. A longitudinal study of a defined population showed that the ocular status of most patients with ocular onchocerciasis remained stable or improved over the 5 year period, particularly in lightly infected cases. The evolution of ocular onchocerciasis showed a deterioration in a minor proportion, restricted to cases of already existing severe lesions, resulting in blindness. A comparison of ophthalmic data from adjacent areas without vector control, indicates that a five year period of vector control may reduce the risk of developing eye lesions or blindness due to onchocerciasis by 50%.

Adolescent↗
PubMed1980

A three-year follow-up of ocular onchocerciasis in an area of vector control.

An evaluation of the effects on onchocerciasis of a 3-year period of vector control was undertaken during 1978 in the Onchocerciasis Control Programme area in West Africa. The results revealed that the overall prevalence of ocular onchocerciasis showed only a slight decrease at the follow-up in 1978, but that there was significantly less infection among children in the age group 5-14 years as compared with 1975. There was a total incidence of ocular signs of onchocerciasis of 8.6% over the 3 years, but also a disappearance of those signs in 11.7% of the sample examined. The incidence of severe onchocercal eye manifestations was low, compared with similar areas of uncontrolled transmission. The particularly low incidence of sclerosing keratitis may be associated with the finding of a significantly decreased microfilarial load in the cornea, whereas the number of living microfilariae in the anterior chamber of the eye was apparently unchanged. The incidence of blindness due to onchocerciasis was low and confined to individuals who already presented severe eye manifestations of the disease before the beginning of the vector control campaign.

Adolescent↗
PubMed1994

[ Onchocerciasis control program in West Africa: socioeconomic development and risk of recrudescence of transmission. 1. Experimental study of the transmission of Onchocerca volvulus strains from Southwestern Sierra Leone by Simulium sirbanum].

As part of the return of savanna migrants installed since a long time in forest regions, in the south of Sierra Leone, we carried out an experimental study about a cross-transmission between Simulium sirbanum from Missira (West-Mali) and the forest strain of Onchocerca volvulus in the south-west of Sierra Leone. This study will allow to know if there is a risk of onchocerciasis transmission recrudescence in relation to the reinstallation of these migrants in their native region. Because of the very high limitation to the forest strain of O. volvulus microfilariae output of the peritrophic membrane reduction with savanna black-flies and according to the very low mature parasite out put of S. sirbanum with this strain observed along this experimentation, the forest strain of O. volvulus from the south Sierra Leone appears maladjusted to S. sirbanum, the main vector of onchocerciasis in savanna regions. This observation implicates a very low intensity of transmission for this forest strain by savanna onchocerciasis vectors. The return of savanna migrants in their native region, installed in the south Sierra Leone since several decades, could not be, in a short time, an origin of onchocerciasis recrudescence in savanna regions of the Onchocerciasis Control Programme area cleaned by an effective vector control carried out since 1975 sustained now by a chemotherapeutic treatment reducing the human parasite reservoir. However, the preservation of this acquired necessitates an epidemiological supervision increased, because the interactions between the vector and the parasite for a long time could carry away a mutual adaptation and a sickness recrudescence.

Animals↗
PubMed1993

DIG-ELISA test in onchocerciasis. Serum antibodies and probability of infection.

An immunoenzymatic test (DIG-ELISA) was serologically evaluated for the serodiagnosis of onchocerciasis. Control and infected sera from the onchocerciasis endemic area of Mexico was collected and the donors assessed for onchocerciasis according to parasitological, clinical, and epidemiological data. The sera were submitted to the DIG-ELISA test using a crude extract prepared from O. volvulus adult worms which had been preserved in nodules in 67% glycerol. The test showed a 100% sensitivity with sera from 38 microfilariae carriers and 96% specificity with sera from 133 non-infected people living outside the endemic zone. In addition, seropositivity was 52.9% with samples from non-onchocercotic people living inside the endemic area, while 82.5 and 90.5% of sera from patients with clinical symptoms and subcutaneous nodules, respectively, were positive. A high rate (30%) of cross-reactivity with serum samples from people infected with Wuchereria bancrofti or Brugia timori was obtained, which is in contrast with the low seropositivity rates (7.4%) obtained with sera from patients infected with other parasites. These results suggest that DIG-ELISA test may be a useful serological test for antibody detection in onchocerciasis, especially for epidemiological surveillance of disease, but because of the high cross-reactivity observed, its use must be limited to areas where this parasitic infection does not coexist with other human filariasis. Finally, the arrangement of sera in groups according to the relative likelihood to have onchocerciasis seems to be a useful procedure for evaluation of serological tests.

Antibodies, Helminth↗
PubMed1993

Immunologic cross-reactivity in the pathogenesis of ocular onchocerciasis.

PURPOSE: Onchocerca volvulus, a filarial worm, is a major cause of infectious blindness and inflammatory eye disease. An autoimmune cause for ocular onchocerciasis has been suggested since the identification of a recombinant antigen of O. volvulus that shows immunologic cross-reactivity with a host ocular component of 44,000 M(r). The aim of this study was to establish the distribution of the cross-reactive antigens in both host tissues and the parasite, and to determine if significant autoantibody responses to the host antigen could be detected in infected persons. METHODS: The tissue and organ distribution of the 44,000 M(r) antigen was determined by immunocytochemistry and Western blot analysis. Human autoantibody responses to the ocular antigen were demonstrated by Western blot analysis using sera collected from persons with onchocerciasis, with and without posterior segment pathology, Bancroftian filariasis, and Europeans with no filarial infection. RESULTS: The tissue distribution of the 44,000 M(r) antigen correlates with the sites of pathology in onchocerciasis and antibody reactivity against this antigen could be detected in all persons with onchocerciasis and posterior segment pathology. The antigen is also recognized by sera from persons with Bancroftian filariasis, but not from normal persons. CONCLUSIONS: A role is proposed for immunologic cross-reactivity in the pathogenesis of onchocerciasis and it is suggested that intraocular presentation of the cross-reactive parasite antigen by microfilariae is essential for the development of disease.

Adult↗
PubMed2000

Human onchocerciasis: the essential partnership between research and disease control efforts.

Twenty years ago onchocerciasis was a disease generally ignored by the medical world, except by those who actually worked with the affected people in Africa and Latin America. Now, largely as a result of the success of mass vector control and drug treatment programs, this is a disease management model for developing countries. The recent literature on onchocerciasis has, not surprisingly, mainly focused on various aspects of control. Investigation into the more basic questions is needed to ensure continued effective disease control. The present mass drug control program is based on a single pharmaceutical, ivermectin (Mectizan), which acts almost exclusively on the microfilarial stage of the infection. Efforts are being made to identify other useful drugs; however, no major candidates have yet appeared. The identification of potential biochemical targets for anti-filarial compounds through a better understanding of the biochemistry of these worms is being pursued. The Onchocerca volvulus endosymbiont Wolbachia may provide a target for therapeutic intervention. An improved understanding of the genomics of O. volvulus has made possible the identification of strain differences in the parasites, and an appreciation of the relevance of these strain differences to the clinical disease, onchocerciasis. There is a need for a better understanding of the clinical disease, and the various pathogenic mechanisms that underly the different syndromes. It is particularly important to understand the pathological basis and mechanisms underlying the adverse responses that can occur with chemotherapy. Present control programs now need to be carefully monitored for effectiveness using new assessment tools, such as antigen assays and the identification of organisms in pools of vectors. Current efforts to control onchocerciasis must be coordinated with new chemotherapy-based control programs for other worm diseases that are emerging. The results of laboratory studies are increasingly being applied to improve the effectiveness of field-based control programs and their assessment. Such research is essential for progress towards the goals of controlling and eliminating onchocerciasis.

Journal Article↗