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Onchocerciasis diagnosis and the probability of visual loss in patients with skin snips negative for Onchocerca volvulus microfilariae.

Two methods have been used to verify the diagnosis of patients living in the onchocerciasis hyperendemic region of Liberia found to have O.v. negative skin snips. The first was based on a histological and an electronmicroscopic examination of the skin to determine whether the characteristic onchocerciasis dermatitis was absent, and to compare the results with age matched subjects having minimal to densely O.v. mf infested skin. The second method involved the skin response of patients with O.v. mf negative skin snips to topically applied DEC. No O.v. mf were found in skin snips serially sectioned and examined histologically from patients in which the results of incubation studies were completely negative. Skin snips from these seemingly O.v. mf negative patients had a dermatitis, whereas no dermatitis was found in skin snips taken from subjects living in nearby nonendemic areas. Patients with O.v. mf positive skin snips responded to DEC applied topically with increased pruritus and a papular rash whose severity was proportionate to the intensity of infestation. Patients with O.v. mf negative skin snips responded to DEC applied topically with increased pruritus and developed either a localized papular rash or widely dispersed papules; confirmation of onchocerciasis in these patients was found in the identification of O.v. mf in histological sections of the papules.

Adolescent↗

The collagenase technique: how to isolate and examine adult Onchocerca volvulus for the evaluation of drug effects.

The collagenase technique developed more than twelve years ago has successfully been applied to isolate living and intact O. volvulus from excised onchocercomata for various biological, morphological, biochemical, immunological and in vitro studies. The experience gained with this technique and its modifications is critically reviewed giving practical advice for the selection, preservation and treatment of nodules for different purposes, especially for the evaluation of antifilarial drug effects. The composition of the worm load, the morphology of adult worms found in untreated patients, signs of degeneration and ageing of worms are described to show the broad morphological spectrum of the worm population in endemic areas to avoid false conclusions in drug trials. When these parameters are carefully considered, the collagenase technique provides a reliable method for examination of onchocercomata. An immediate answer can be obtained concerning the viability of the parasite. The qualitative and quantitative assessment of reproduction (embryogram) can give further valuable information on any changes in the reproductive dynamics and provide a sensitive indicator of any disturbances in the adult worms which may explain the early or late reinvasion of microfilariae into the skin after treatment with microfilaricidal drugs.

Animals↗

The populatin dynamics of Onchocerca volvulus microfilariae during treatment with suramin and diethylcarbamazine.

During treatment with suramin the numbers of O. volvulus microfilariae in the blood, urine, sputum, and anterior chambers of the eye fell before those in the skin. When diethylcarbamazine (DEC) was given after suramin, increased numbers of microfilariae appeared in the blood, urine, cerebrospinal fluid (CSF) and sputum, but the increase in the blood was less marked, and of shorter duration, than in similar patients receiving DEC without previous suramin. Microfilariae are thought to enter the urine, sputum and CSF directly from the blood by penetrating the capillary walls in the glomeruli, pulmonary alveoli, and choroid plexuses. Those in the aqueous humour do not appear to come directly from the bloodstream. The total numbers of microfilariae in the skin of some heavily infected onchocerciasis patients are estimated, as are the total numbers moving into the blood-stream under the influence of DEC and the proportion which escape into the urine, sputum and CSF. It is concluded that the majority of the microfilariae which appear in the blood during DEC therapy must be destroyed in the body, probably in the liver.

Anterior Chamber↗

Epidemiological impact of vector control. I. Incidence and changes in prevalence and intensity of Onchocerca volvulus infection.

Since 1974, the Onchocerciasis Control Programme (OCP) has been engaged in a large scale attempt to control the savanna species of the vector of onchocerciasis in seven West African countries. The effect of the vector control effort has been measured by epidemiological evaluation. For this purpose 474 villages have been examined by means of skin snip surveys between 1975 and 1983 and of these, 184 have been retained to-date for follow-up surveys which have documented over the years the reduction of the parasite population. The latest results of the epidemiological evaluation clearly demonstrate an outstanding success of the vector control campaign. The parasite has been or is close to being eliminated from the hyperendemic foci of the core area of the Programme. Major improvements have been registered in the reinvaded areas located at the Western and Eastern borders of the Programme. A major improvement has been found along the river Marahoué, the only focus of the intermediate area between the savanna and the forest where at the previous survey, the endemic situation was still similar to the pre-control situation. The exceptions to this gratifying picture are foci along the Dienkoa and Kulpawn rivers, both located in the core area, where transmission has relapsed and several more years of an effective vector control will be needed to eliminate the local parasite population.

Adult↗

Identification of different radiolabelled antigens of the developmental stages of Onchocerca volvulus.

By using radioiodination methods which are thought to label preferentially the surface followed by SDS-PAGE and autoradiography, components of different developmental stages of O. volvulus have been identified. Between 2 and 10 polypeptide antigens were revealed on infective larvae (L3), females, males, eggs, nodular and skin microfilariae by using immunoblotting assays with human onchocerciasis sera. Antigen recognition did not vary with the density of skin microfilariae in the patients from whom the sera were obtained. Some of the antigens seemed to be stage specific; for example, antigens of 31 kDa which were detected only on skin microfilariae, or the 67.5 and 25 kDa components that occurred on the adult females, but were absent from adult males. Some of these antigens were also identified as glycoproteins. A 68 kDa glycoprotein was found in adult females, males and nodular microfilariae. Two glycoproteins of 74 and 45 kDa were found on egg shells, and a 18.5 kDa glycoprotein was recovered from L3. Type VI collagen was found with a specific antiserum on skin microfilariae, but not on eggs and females. Laminin was found on nodular mf. It is concluded that the changing antigenic profiles of the worm stages and the coating of these worms with connective tissue epitopes contribute to the evasion of host immunity.

Animals↗

A community trial of ivermectin in the onchocerciasis focus of Asubende, Ghana. I. Effect on the microfilarial reservoir and the transmission of Onchocerca volvulus.

A community trial of the microfilaricide ivermectin was undertaken in an isolated focus of hyperendemic savanna onchocerciasis in Ghana. One of the objectives was to determine the effect of mass treatment on the microfilarial reservoir and on the transmission of Onchocerciasis volvulus. Since 1978 the focus has been under entomological surveillance. This was intensified from 1 September 1987 till 11 February 1988 with daily vector collection and dissection of over 30,000 flies. A total of 14,991 people were treated with ivermectin on 7-10 October 1987. Skin snip surveys were done pre-treatment, and at two and four months after treatment. The mean skin microfilarial load in treated persons had fallen by more than 96% two months after treatment. During the next two months there was an increase in microfilaria loads which appeared to be faster than reported in the clinical trials. The total reservoir of skin microfilariae available for transmission had been reduced by an estimated 68%-78% two months after treatment. This was consistent with the entomological results which indicated a reduction in transmission of 65%-85% during the first three post-treatment months. The present study has shown for the first time that mass chemotherapy can significantly reduce onchocerciasis transmission. However, the remaining level of transmission was still unacceptably high and further studies are required to predict the long term impact of repeated mass treatment.

Animals↗

Observations on the reproductive biology of Onchocerca volvulus.

This study compiles observations on the reproductive capacity of O. volvulus. Adult parasites enzymatically isolated from excised onchocercomata of untreated and chemotherapeutically treated patients, and from inhabitants living in areas with long vector control, were investigated to assess their fecundity. Changes of microfilaria development in utero and microfilaria release were assessed or estimated after treatment of patients with micro-filaricidal drugs that interfered with the development of intra-uterine stages. Intra-uterine production of microfilariae: After treatment of patients with ivermectin a daily development of 2500 to 4000 uterine microfilariae per female worm was observed. Actual output of microfilariae: Microfilariae left actively the female worms. The daily microfilaria release in vivo was 700 to 900 microfilariae, assessed after treatment of patients with mebendazole. In vitro most worms isolated from untreated patients shed between 500 to 1500 microfilariae per day.-The microfilarial load of 56 adult patients calculated from microfilarial skin counts was 12 million on the average. Taken for granted a mean life span of a microfilaria of 1.0 to 1.5 years, 22 to 47 female worms per patient would suffice to maintain this microfilarial load on a constant level. Excision of all palpable nodules showed a geometric mean of 15.9 female worms in these patients. It is suggested that factors intrinsic in the host and the adult worms partially operate together to regulate and maintain a stable microfilarial density.

Animals↗

Studies on nodules and adult Onchocerca volvulus during a nodulectomy trial in hyperendemic villages in Liberia and Upper Volta. II. Comparison of the macrofilaria population in adult nodule carriers.

In the Liberian rain-forest and the savanna of Upper Volta 189 adult nodule carriers were operated on. From 2231 extirpated nodules 3327 male and 5713 female macrofilariae were isolated. About 98% of the male worms and 88% of the female worms were found alive. The sex ratio of the live male and female worms was 1:1.5 in Liberia and 1:1.6 in Upper Volta. Less than 1% of all live macrofilariae were immature in both countries. 22% of the live male worms in Liberia were regarded as old. The percentage of old male and female worms in Upper Volta and that of the old female worms in Liberia were similar (5-7%). The portion of old worms was independent of the age of the patients in Liberia. Dead worms were found in 66% of the Liberians and in 85% of the Voltaics. The percentage of patients with dead worms increased with the age. About 0.5% of all male and 8% of all female worms were calcified. In Liberia the percentage of calcified worms increased with the age of the patients. In both countries the highest number of live and dead worms were found on the pelvic girdle. On the thorax many more macrofilariae were found in Upper Volta than in Liberia. This may contribute to the severe eye lesions in this savanna area. The presented findings provide some basic information for the planning and performance of trials with macrofilaricidal drugs in hyperendemic areas of West Africa. However, the striking differences between individual worm burdens have to be considered.

Adolescent↗

Ivermectin: reduction in prevalence and infection intensity of Onchocerca volvulus following biannual treatments in five Guatemalan communities.

Residents of five hyperendemic communities located in the central focus of onchocerciasis in Guatemala were treated with ivermectin (Mectizan) or placebo every six months for 30 months. The effects of treatment on prevalence and the intensity of skin infection (microfilarial skin density [MFD]) were evaluated. Significant and persistent reductions in both of these indices were achieved by coverage of 80.7% of the eligible populations. The highest proportionate reductions in both indicators of infection occurred after the first treatment, followed by more gradual decreases through the fourth treatment. In one community in which the mean coverage was 92.7%, prevalence decreased from 74.0% at pretreatment to 34.9% after four treatments, while the MFD decreased from 7.8 to 2.0; reductions of 52.8% and 74.3% from pretreatment values, respectively. In every ivermectin-treated community except one, in which drug acceptance was low, the mean community MFD values were reduced to the level associated with low infectiousness for the vector, Simulium ochraceum. Moreover, the category of MFD associated with high vector infectiousness was reduced at least ten-fold over the pretreatment level. One community had low participation during the first two treatments (32.8% and 22.7% of those eligible). This increased to 55.2% at the third treatment because of implementation of an educational program describing both the disease and the beneficial effects of ivermectin and because skin biopsies and nodulectomies were not performed. Secondary reaction rates for all communities were 29.5%, 9.9%, 10.3%, 8.2%, and 7.1% for the first through fifth treatments, respectively. Pruritus was the most common (34.0%) secondary reaction, followed by facial edema (31.8%). All reactions were classified as mild to moderate. Recommendations for mass distribution of ivermectin in Guatemala are given.

Adolescent↗

Onchocerciasis in Malawi. 2. Subjective complaints and decreased weight in persons infected with Onchocerca volvulus in the Thyolo highlands.

In the course of an onchocerciasis survey in southern Malawi, body weight was recorded for 10,335 persons aged 20 years and older, and the body mass index was calculated for 5572. A history of symptomatic complaints was elicited from 5653 persons 20 years of age and older. Persons with microfilariae in the skin snips weighed significantly less than persons with negative skin snips. Symptomatic complaints of musculoskeletal pains, itching, dizziness and poor vision were reported more commonly in the group with microfilariae. These findings suggest that onchocerciasis should no longer be considered a disease affecting the eye and skin only but an infection which produces systemic effects as well. Systemic effects of onchocerciasis may lessen productivity of an endemic region by a process distinct from the effects of visual impairment.

Adult↗