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PubMed2003

Impact of ivermectin on onchocerciasis transmission: assessing the empirical evidence that repeated ivermectin mass treatments may lead to elimination/eradication in West-Africa.

BACKGROUND: The Onchocerciasis Control Program (OCP) in West Africa has been closed down at the end of 2002. All subsequent control will be transferred to the participating countries and will almost entirely be based on periodic mass treatment with ivermectin. This makes the question whether elimination of infection or eradication of onchocerciasis can be achieved using this strategy of critical importance. This study was undertaken to explore this issue. METHODS: An empirical approach was adopted in which a comprehensive analysis was undertaken of available data on the impact of more than a decade of ivermectin treatment on onchocerciasis infection and transmission. Relevant entomological and epidemiological data from 14 river basins in the OCP and one basin in Cameroon were reviewed. Areas were distinguished by frequency of treatment (6-monthly or annually), endemicity level and additional control measures such as vector control. Assessment of results were in terms of epidemiological and entomological parameters, and as a measure of inputs, therapeutic and geographical coverage rates were used. RESULTS: In all of the river basins studied, ivermectin treatment sharply reduced prevalence and intensity of infection. Significant transmission, however, is still ongoing in some basins after 10-12 years of ivermectin treatment. In other basins, transmission may have been interrupted, but this needs to be confirmed by in-depth evaluations. In one mesoendemic basin, where 20 rounds of four-monthly treatment reduced prevalence of infection to levels as low as 2-3%, there was significant recrudescence of infection within a few years after interruption of treatment. CONCLUSIONS: Ivermectin treatment has been very successful in eliminating onchocerciasis as a public health problem. However, the results presented in this paper make it almost certain that repeated ivermectin mass treatment will not lead to the elimination of transmission of onchocerciasis from West Africa. Data on 6-monthly treatments are not sufficient to draw definitive conclusions.

Journal Article↗
PubMed1997

[Endemicity and clinical manifestations of onchocerciasis in the province of Bururi, Burundi].

A sample of the population of 20 'collines' (administrative units) of the province of Bururi (Burundi, Central Africa) was examined to determine the prevalence and intensity of onchocerciasis in this endemic region. In all, 34.4% of the population is infected, that is about 80,000 people for the whole area. Around Rumonge onchocerciasis is hyperendemic. This area is surrounded by a mesoendemic zone and at the periphery onchocerciasis is hypoendemic. The clinical examination of a subsample showed that pruritus and skin lesions are not very frequent (58.2 and 28.1% respectively in positive persons). Subcutaneous nodules are small and difficult to find (21.3% in positive cases). Vision is 10/10 in 92.2% of the examined eyes. A slight drop in visual acuity may be attributed to onchocerciasis in 9.4% of positive cases.

Adolescent↗
PubMed1990

The onchocerciasis focus at Kinsuka/Kinshasa (Republic of Zaire) in 1985. II. Parasitological and clinical aspects.

Since the antivectorial control in 1948, the parasitological and clinical aspects of the onchocerciasis focus at Kinsuka/Kinshasa have not been studied further until now. The population examined was selected for its daily contact with the vector. It constituted 143 adults, including fishermen, stonebreakers and women cultivators, and 26 children aged from 10 to 16 years. People were subjected to an ophthalmological examination as well as to an investigation for Onchocerca volvulus microfilariae. Adults were examined for the presence of nodules as well as for dermal and lymphatic manifestations of onchocerciasis. The microfilaria carrier rate (MfCR) was 59.2%. The mean microfilaria density (MfD) was 9.7 mf mg-1. Only 20% of the adults presented with small onchocercal nodules. Cutaneous lesions were mild. Lymphatic complications such as adenolymphocele, hydrocele and elephantiasis of the lower limbs were observed in 18% of the adults. No one was blind from onchocerciasis, although nine patients of 60 years or over had lost the use of one eye. Punctate keratitis occurred commonly in young people. Ocular lesions, except for punctate keratitis, developed progressively after 55 years and they became worse with the degree of infection, age and length of stay. Hyperendemic and insufferable in 1940, onchocerciasis has become, in 1985, hypoendemic and no longer a public health problem. One could deduce that a situation similar to that in Kinsuka may occur within 30 years in other foci which are today hyperendemic and where prophylaxis has been started.

Adolescent↗
PubMed1993

A study of onchocerciasis with severe skin and eye lesions in a hyperendemic zone in the forest of southwestern Cameroon: clinical, parasitologic, and entomologic findings.

Prior to the initiation of an onchocerciasis control program based on the mass administration of ivermectin in the rain forest of southwestern Cameroon, a preliminary baseline study of the area was conducted. The results of this study showed that onchocerciasis was hyperendemic in the area. Skin symptoms and signs were observed including pruritus (67.4% of the population examined), onchocerca nodules (51.6%), skin depigmentation (18.5%), and hanging groins (5.7%). Except for pruritus, the prevalence of these symptoms increased with age. Of the eyes examined, 44.9% had microfilariae in the anterior chamber, 33.5% had choroidoretinitis, 28.0% had punctate keratitis, 8.3% had papillary abnormalities, and 3.6% had sclerosing keratitis. Vision in 10.5% of the eyes examined was classified as blind or very poor (visual acuity = 0-0.10), in 15.7% as poor (visual acuity = 0.11-0.39), and in 73.8% as good (visual acuity = 0.4-1.00). Unlike previous reports that have linked serious ocular damage mainly to savanna onchocerciasis, the present study showed that forest onchocerciasis also caused significant ocular pathology, including blindness. Parasitologically, positive skin snips were recorded for 92.7% of the persons examined, with both sexes being equally infected. The parasite load, expressed as the geometric mean number of microfilariae per skin snip, was 53.6, and was much higher in males than in females. The flv vector, Simulium squamosum, had a high infection rate of 7.5% infective females in Bakumba and 6.8% infective females in Ngbandi, the two fly-catching points. The transmission potential was 266 infective larvae per person per month in Bakumba and 189 in Ngbandi.

Adolescent↗
PubMed1990

[Study of the transmission of onchocerciasis in the surroundings of a refugee camp located in the savanna zone of Cameroon].

Chadian refugees, most of whom are free from onchocerciasis, settled recently in a camp in a savanna area of the northern Cameroon where the prevalence is about 80% and the blindness rate is 4% of the adult population. In view of the risks of onchocerciasis facing the immigrants, the authors carried out an entomological survey in this region aimed at determining the modes of transmission and assessing the possibilities for the control of this disease. After a three-month survey in the study area, it appears clearly that 1) transmission takes place only during the rainy season, 2) the main vectors are the two savanna species, Simulium damnosum s.s. and Simulium sirbanum, 3) the larval breeding sites are not located on the principal river, the Faro, but on its small seasonal tributaries, 4) the local populations still free from onchocerciasis and the Chadian refugees who farm close to these tributaries run the risk of getting serious ocular lesions in the long run which could lead to blindness. The conclusions of this survey prompted the authors to envisage an onchocerciasis control campaign in this area against the larval stages of the vectors.

Animals↗
PubMedDate not supplied

[The use of ivermectin in the control of onchocerciasis].

Onchocerciasis is an infection with the nematode Onchocerca volvulus. The main clinical symptoms are caused by the microfilariae. They include ocular lesions leading to blindness. Onchocerciasis is widely distributed in Africa from the Sahara to the southern tip, and is also found in some areas of South and Central America. Ivermectin was shown to be an effective treatment in the early 1980's, and is safe and better tolerated than diethylcarbamazine. We report the results of ivermectin treatment of onchocerciasis, and various features of the control obtained by large-scale ivermectin treatment programs. In large-scale programs, ivermectin (150 micrograms/kg) is administered once a year. This dose paralyses the microfilariae, such that they are carried away by the lymph to the lymph nodes where they are destroyed. This dose thereby reduces the load of microfilaria by 90%. The effects of a dose of ivermectin last about two or three years, and the lesions in the anterior segment of the eye can be cured or substantially reduced. Regular treatment prevents severe lesions of the posterior segment of the eye. The effects of repeated treatment on lesions of the retina are currently under investigation. Frequent doses of ivermectin prevent the development of embryo parasites in the females, and reduces the number of adults by attrition. Large-scale treatment programs reduce the transmission of the parasite by its vectors. There are several problems impeding large-scale treatment programs. Choosing patients for priority treatment requires expensive and sometimes aggressive methods of diagnosis. Thus new techniques for the identification of communities in which onchocerciasis is a serious public health problem are required. The choice of strategies for distribution, to optimize the cost, benefit ratio and feasibility, remain controversial. Wide distribution by mobile teams is effective, but expensive. Active distribution by trained community distributors is a cheaper potential alternative. Clinic-based or passive distribution requires the population to present to be able to obtain ivermectin. Thus, although cheap, this approach is generally poorly effective. A further complication is the clearly defined criteria on which these methods should be evaluated.

Africa↗
PubMed1997

[Endemic disease and clinical manifestations of onchocerciasis in the province of Rutana (Burundi)].

In 9 'collines' (administrative units) of the province of Rutana (Burundi) a sample of the population was examined to determine the prevalence and intensity of onchocerciasis in this endemic region. In all, the area is hypoendemic with 7.9% of the population infected. This means that, in a population of 52,000, about 4000 persons are parasitised. The intensity of onchocerciasis is low, in general. Clinical examination in a subsample of 4 collines showed that the number of people with onchocerciasis who complain about pruritus or who have skin lesions is limited (respectively 54.4% and 38.1%). Subcutaneous nodules are small and difficult to detect (20.6% in positive persons). Ocular damage, as measured by visual acuity, is minimal: 89.9% of the examined eyes had a visual acuity of 10/10. Amongst positive persons, 23.6% had a slightly deteriorated vision (between 9/10 and 3/10) which might be attributed to onchocerciasis.

Adolescent↗
PubMed1987

Onchocerciasis--a potential revolution in its treatment.

Onchocerciasis is a major blinding disease affecting at least 28 million people in Africa and Latin America. Although a large-scale vector control program has been highly successful in limiting transmission of infection in West Africa, there has not been a satisfactory form of treatment available for those already infected or those living in other areas. Despite the fact that two drugs, diethylcarbamazine and suramin, are active against the filarial parasite that causes onchocerciasis, their use is severely limited by their toxicity and the reaction they induce. A newly developed drug, ivermectin, appears to offer a major revolution in the treatment of onchocerciasis. In a series of clinical trials, ivermectin has been shown to be an extremely effective microfilaricide which induces only minimal side effects. Ivermectin is given as a single oral dose which can be repeated on an annual basis. In view of its safety and efficacy and its ease of administration, it seems likely that ivermectin will be suitable for use in mass chemotherapy programs against onchocerciasis.

Eye Diseases↗
PubMed1986

Schoolchildren and ocular onchocerciasis in the rain-forest of Cameroon.

The results of surveys among 188 primary school children in two hyperendemic rain-forest villages in South-West Cameroon are reported. The children were examined for their nutritional state and for lesions due to onchocerciasis, with emphasis on eye pathology. Clinical manifestations in the two villages hyperendemic for onchocerciasis were compared with those found in a hypo-endemic coastal village. The primary school age appeared to be the period with the highest increase in ocular, notably corneal, involvement in onchocerciasis. The prevalence of ocular involvement showed an increase from 42.8% in the 6-year age group to 100% in the 12-year age group. 17.5% of the children were considered to be at risk of developing serious ocular onchocerciasis. Significant correlation between nutritional state and severity of infection could not be demonstrated. Sex differences in onchocercal symptomatology appeared not to be significant. The importance of microfilarial concentration in the skin snip near the eye is stressed as a simple but important indicator of danger to the eye. Prognosis and therapy are discussed.

Adolescent↗
PubMed1987

Distribution pattern of peripheral lymphocyte subsets in localized and generalized form of onchocerciasis.

The relationship of peripheral lymphocyte subpopulations to the generalized and localized form of onchocerciasis has been studied in 43 Liberian (West African) patients. Typing revealed a significantly increased proportion of lymphocytes expressing interleukin 2 or transferrin receptors in the localized form of onchocerciasis (African sowda) when compared to subjects with a generalized form and those without signs of onchocerciasis. Patients with African sowda showed a higher number of helper/inducer T cells, a greater ratio of helper/inducer: suppressor/cytotoxic T cells, and an increased number of DR antigen-positive cells and lymphocytes with a natural killer cell phenotype. Furthermore, the serum concentrations of immunoglobulins, particularly IgE an IgG, and antifilarial antibodies were significantly elevated in sowda patients in comparison to the generalized form and the controls. These results indicate that both forms of onchocerciasis represent different immunological types of host responsiveness and that African sowda might be associated with an increased compartment of activated T lymphocytes.

Antibodies, Monoclonal↗
PubMed1991

Knowledge, attitudes and perceptions (KAP) of onchocerciasis: a survey among residents in an endemic area in Guatemala targeted for mass chemotherapy with ivermectin.

If ivermectin distribution programs are to have maximum impact on the morbidity and transmission of human onchocerciasis there must be broad and sustained acceptance within the endemic communities. Educational activities, developed with careful consideration of community attitudes, should promote positive treatment seeking behavior while simultaneously addressing local reservations about the control effort. To better understand the ambient knowledge, attitudes, and practices concerning onchocerciasis in the context of ivermectin use in Guatemala, we conducted a survey among 145 heads of households in five endemic communities. Given the country's long-standing nodulectomy program, it was not surprising that 100% of persons interviewed had heard of the disease 'la filaria', which they defined as a skin nodule that could cause blindness. Ninety-five percent of respondents identified surgery as the only cure for the condition. Relatively few (39%) knew that la filaria was caused by a worm, although slightly more (50%) knew that the condition was acquired by the bite of an insect. The term microfilaria was not broadly recognized. We also determined that onchocerciasis was not perceived as a serious health problem: few persons (12%) mentioned la filaria when requested to provide a complete list of illnesses that occurred in the community, and the gravity of infection (based on rank ordering of common illnesses) was similar to that of a bad cold. Recommendations were made which might assist long-term acceptance of a national chemotherapy initiative against onchocerciasis in Guatemala.

Adolescent↗
PubMedDate not supplied

Onchocerciasis--river blindness.

Onchocerciasis results from infestation by the nematode Onchocerca volvulus and is characterized by troublesome itching, skin lesions, and eye manifestations. Although partially controlled by international mass prevention programs, onchocerciasis remains a major health hazard and is endemic in Africa, Arabia, and the Americas. Onchocerciasis is spread by bites from infested black flies, which transmit larvae that subsequently develop into adult filariae. Skin symptoms are commonly nonspecific and include severe pruritus, acute and chronic dermatitis, vitiligo-like hypopigmentation, and atrophy. Onchocercal ocular disease covers a large spectrum of manifestations, which in severe cases, may lead to blindness. Diagnosis is usually made by direct visualization of the larvae emerging from superficial skin biopsies, "skin snips." In some cases, the microfilariae can also be directly observed at the slit lamp when migrating into the anterior chamber of the eye. Ivermectin is, at present, the drug of choice for skin and ocular manifestations. Recent research using a chemotherapeutic approach that targets filarial Wolbachia symbionts in the treatment and control of onchocerciasis, however, suggests that 100 mg/d of doxycycline for 6 weeks might be effective in reducing the filarial load and preventing ocular symptoms.

Humans↗
PubMed1999

Eosinophils, eosinophil cationic protein and eosinophil-derived neurotoxin in serum and urine of patients with onchocerciasis coinfected with intestinal nematodes and in urinary schistosomiasis.

Eosinophils, eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN/EPX), myeloperoxidase (MPO) and IgE were measured in blood, serum and/or urine in Schistosoma haematobium- and Onchocerca volvulus-infected Guineans and O. volvulus- and S. haematobium-negative Guineans coinfected or infected with intestinal nematodes. The number of eosinophils and levels of eosinophil granule proteins but not of MPO were found to be strongly elevated in all Africans as compared to European controls. The highest serum ECP and serum and urinary EDN/EPX levels were observed in the hyperreactive form of onchocerciasis (sowda). Onchocerciasis patients and O. volvulus-negative Africans coinfected or infected with intestinal nematodes (hookworm and/or Ascaris lumbricoides) revealed higher serum granule protein concentrations and/or absolute eosinophil counts and urinary ECP than those without nematode infections. Statistical differences between both sections were found for the absolute eosinophil counts and for serum EDN/EPX and IgE in generalized onchocerciasis, and for urinary ECP in sowda, indicating stimulation of the eosinophil potential of O. volvulus-positive patients by coexistent hookworm infection. This worm species, in contrast to A. lumbricoides, causes especially high eosinophil counts and EDN/EPX and IgE levels. From these results it is concluded that in nematode diseases, ECP and EDN/EPX levels reflect the degree of antigenic stimulation, eosinophil activation and eosinophil turnover rates. Serum ECP and serum and urinary EDN/EPX may, therefore, serve as parameters to monitor helminth infection. Urinary ECP may be a marker of eosinophiluria secondary to urogenital manifestation of S. haematobium. It is elevated in hyperreactive onchocerciasis activated by intestinal nematodes.

Adolescent↗
PubMedDate not supplied

Topical application of diethylcarbamazine to detect onchocerciasis recrudescence in west Africa.

The Onchocerciasis Control Programme in West Africa (OCP) has succeeded in eliminating blinding onchocerciasis as a public health problem throughout much of West Africa. The efforts of the OCP are now turning towards surveillance, with the goal of rapidly detecting and controlling outbreaks of infection in the onchocerciasis-free zone. With this goal in mind, cutaneous application of a solution of diethylcarbamazine (the DEC-patch test) was evaluated in 1996-99 as a method to detect patent Onchocerca volvulus infection in children and adolescents, a sentinel population for the detection of recrudescence. In an analysis of 1887 individuals in Côte d'Ivoire and Burkina Faso, the DEC-patch test produced prevalence estimates comparable to those obtained by skin snip. The sensitivity of the DEC-patch assay was marginally greater in children and adolescents than in adults, and was greater in individuals who had received prior Mectizan treatment. These data suggest that the DEC-patch test may be a useful tool for detecting recrudescence of O. volvulus infection in a sentinel population of children and young adults within the onchocerciasis-free zone created by the OCP.

Administration, Cutaneous↗
PubMed2002

The variant Arg110Gln of human IL-13 is associated with an immunologically hyper-reactive form of onchocerciasis (sowda).

Onchocerca volvulus infection usually results in a predominantly immunopermissive reaction called generalized onchocerciasis and characterized by high microfilarial burden and immunological tolerance to the worms. Rarely, however, infection leads to the sowda form of the disease displaying low microfilarial numbers, i.e. microfilarial control, and a T helper 2 (Th2)-type immune response including high immunoglobulin (Ig)E levels, and interleukin (IL)-13 being one of the key cytokines. The aim of this study was to investigate a possible association of a variant of the IL-13 gene, which confers an IgE-independent risk for asthma and atopy, with the immunologically hyper-reactive sowda form of onchocerciasis. Genotyping for the IL-13 variant Arg110Gln revealed a highly significant association of Arg110Gln with the sowda form (relative risk of 2.98, n = 19 patients), whereas the frequency of the variant was significantly lower in patients with generalized onchocerciasis (n = 92 individuals). Sowda patients had higher IgE levels than those with generalized onchocerciasis. Logistic regression analysis revealed that IgE and IL-13 are independent variables, each increasing the relative risk for sowda. Arg110Gln has been suggested to lead to enhanced IL-13 signaling and thus may be involved in shifting the immune reaction towards the hyper-reactivity characteristic for the sowda form, thereby promoting defense mechanisms.

Alleles↗
PubMed2003

Doxycycline in the treatment of human onchocerciasis: Kinetics of Wolbachia endobacteria reduction and of inhibition of embryogenesis in female Onchocerca worms.

Recently, experts have warned that mass treatment with ivermectin alone may not interrupt the transmission of Onchocerca. Hence, additional drugs are needed, such as antibiotics acting on symbiotic endobacteria of the filariae, the causative agents of onchocerciasis. Based on animal experiments, human onchocerciasis was treated with doxycycline, and preliminary observations published in 2001 in The Lancet showed sterility in female worms by depletion and marked reduction in symbiotic Wolbachia endobacteria from the filariae. Here, a detailed kinetic analysis of the features of the worms, following administration or not of doxycycline to the patients is reported. Sixty-three onchocerciasis patients in Ghana were treated with 100 mg doxycycline daily for 6 weeks and 2 or 6 months later with ivermectin. Onchocercomas were extirpated 2, 6, 11 and 18 months after the onset of treatment and the filariae were examined by immunohistology and PCR. The analysis showed: (i) progressive depletion of Wolbachia from adult worms and microfilariae by doxycycline over a period of 6 months; (ii) inhibition of embryogenesis by doxycycline after 6 months with respect to all embryo stages followed by decline in microfilariae after 11 months; (iii) reduction in spermatozoa in the female genital tract by doxycycline, whereas spermiogenesis was only partly reduced after 11 and 18 months; (iv) no relevant macro- or microfilaricidal activity; (v) depletion/marked reduction in endobacteria and inhibition of embryogenesis were sustained until 18 months after doxycycline and 12 months after co-administration of ivermectin; (vi) no severe adverse side effects were seen. Due to its long-lasting inhibition of embryogenesis, doxycycline presents an additional strategy for the treatment of onchocerciasis and control of Onchocerca microfilariae transmission. Extension of the existing registration will not require much time or high cost. Treatment of individual patients can be considered immediately.

Animals↗
PubMed1986

A study on antigen recognition by onchocerciasis patients with different clinical forms of disease.

Sera from 40 onchocerciasis patients from the Yemen Arab Republic with either mild localized forms of onchocerciasis, intermediate or severe localized forms of the disease or generalized forms of infection were studied with respect to their IgG and IgM response against Onchocerca volvulus antigens. Immunoblotting, performed with SDS-PAGE-separated proteins of female O. volvulus and quantified by densitometric scanning, revealed IgG and IgM antibodies against worm components in sera of all patients. Persons with intermediate or severe localized forms of onchocerciasis had a stronger IgG response against more proteins than individuals of the other groups. However, some antigens (Mr 21, 23, 30, 33 kDa) induced comparable quantities of IgG in all groups. The IgM response of patients with mild localized forms of onchocerciasis was more intensive and directed against more antigens than in the other groups. No antigens were detected that were recognized only by individuals with low levels of microfilaridermia. In all groups, varying concentrations of antibodies against cuticle, muscle/hypodermis layer and/or uterus of female O. volvulus were detected by the indirect immunofluorescence test using frozen worm sections as antigen. The highest mean antibody titres were found in patients with intermediate and severe localized forms of disease.

Adult↗
PubMed2003

Profile of eye lesions and vision loss: a cross-sectional study in Lusambo, a forest-savanna area hyperendemic for onchocerciasis in the Democratic Republic of Congo.

OBJECTIVE: To determine baseline data regarding eye lesions and vision loss in five villages of Lusambo, an onchocerciasis-hyperendemic forest-savanna area in the Democratic Republic of Congo (DRC), in preparation of mass ivermectin distribution. METHODS: Five villages were selected by simple randomization. Through a cross-sectional design, 750 subjects were examined ophthalmologically. The eye examination included acuity visual measurement, slit-lamp examination, ophthalmoscopy, intraocular pressure measurement, and visual field assessment by the Wu-Jones test. RESULTS: There was a high prevalence of onchocerciasis-related eye lesions compared with non-onchocercal lesions. Chorioretinitis (20%) was the most frequent disease, others were punctate keratitis and microfilariae in the anterior chamber in equal frequency (13.8%), white intraretinal deposits (10.4%) and iridocyclitis (8%). Vision loss was discovered in 8.5% of the subjects, of whom 0.5% had bilateral blindness, 2.2% had monocular blindness and 5.7% had visual impairment. Vision loss was mostly caused by onchocerciasis-related diseases, especially those affecting the anterior segment of the eye. CONCLUSION: Features of ocular onchocerciasis usually described in forest and savanna areas were both found in this forest-savanna zone of the DRC.

Adolescent↗