Effect of repeated ivermectin treatments on ocular onchocerciasis: evaluation after six to eight doses.

In 26 villages (1987 population 12,302), hyperendemic for savanna onchocerciasis in North Cameroon, ivermectin was distributed annually between 1987/89 and 1995. Each year until 1992, ophthalmologic examinations were performed before treatment. A final examination was made in 1995. The effects of ivermectin on ocular onchocerciasis were assessed by following (a) the ophthalmologic indices in three cohorts of males recruited before treatment in 1987, 1988 and 1989, who were treated and examined annually, and (b) the indices recorded yearly in the cross-section of males aged 15-19 years. The indices in 1995 from patients who had received up to eight doses were compared with those calculated before treatment in individuals of similar age. In the cohorts, the prevalences of microfilariae in the anterior chamber (MFAC) and of punctate keratitis (PK) recorded in 1995 were markedly reduced; there was a non-significant decrease in sclerosing keratitis (SK), and a significant worsening in the fundus indices in the cohorts. The cross-sectional analysis showed significant decreases in the prevalences of MFAC, PK and SK, and a significant increase in the mean visual acuity; there was no significant change in any fundus index. The findings suggest that repeated ivermectin treatment does not prevent the appearance of initial retinal lesions or the worsening of existing retinal lesions.

[The effect of ivermectin on the longevity of Simulium damnosum]. / Etude de l'effet de l'ivermectine sur la longévité de Simulium damnosum.

Studies on various blood-sucking arthropods have shown an increased mortality after feeding on hosts previously treated with ivermectin. We investigated in Cameroon the survival of blackflies (Simulium damnosum s.s. and S. sirbanum) fed on patients who had been treated at a dose of 150 micrograms/kg 3-13 days before the blood meal. The mortality rates were not significantly reduced when compared with those of flies fed on untreated individuals.

[Epidemiologic study of the main human intestinal nematodes in the middle west of Madagascar]. / Etude épidémiologique des principales nématodoses intestinales humaines dans le Moyen-ouest de Madagascar.

An epidemiological study of human intestinal helminthiasis was conducted during July and August 1995, in the middle west of Madagascar, with 4571 adults and children ranging from six months to 90 years, in 61 communities between Betafo and Miandrivazo. Faecal examination utilising the MIF concentration method revealed that ascariasis was the dominant nematodosis in the middle west with high prevalences in the high-altitude communities. Ascaris lumbricoides prevalences increase among children and women. Interesting more than 50% of the pattern, ascariasis is a public health problem and its association with infant malnutrition is statistically significant. Hookworm infection prevalence is higher in low-altitude communities, it increases among adults. The Trichuris trichiura prevalences were lower than the prevalences of ascariasis and hookworm infection in all of the communities. Important variations of the prevalences of intestinal helminthiasis are observed essentially in relation with climatic conditions.

Onchocerca volvulus: striking decrease in transmission in the Vina valley (Cameroon) after eight annual large scale ivermectin treatments.

The impact of repeated ivermectin treatments on the transmission of Onchocerca volvulus was evaluated in the Vina valley, northern Cameroon, by comparing the prevalence and intensity of infection observed in untreated 5-7 years old children living in the treated communities before and after 7-8 successive annual rounds of ivermectin treatment of the general population of those communities. The villages studied were Ngoumi and Babidan, where the initial community microfilarial loads (CMFL) were 83.7 and 216.4 microfilariae per skin snip, respectively. In 1995, after 8 annual treatments, the prevalence and intensity in Ngoumi had decreased by more than 90%, compared with the pretreatment values, and the prevalence continued to decrease between 1992 and 1995. In Babidan, after 7 annual treatments, the prevalence and intensity had also decreased significantly, but less than in Ngoumi. The study demonstrated that repeated treatments brought about a notable reduction in the transmission of O. volvulus in the Vina valley, despite unfavourable factors such as mean drug coverages below 60% and the good vectorial competence of Simulium damnosum s.s. and S. sirbanum.

Effect of repeated treatments with ivermectin on the incidence of onchocerciasis in northern Cameroon.

Mass treatments with ivermectin have been undertaken each year since 1987 in an area hyperendemic for onchocerciasis in northern Cameroon. The impact of these successive treatments on the incidence of infection in humans was evaluated by comparing the prevalence of skin microfilariae (PMF) and the mean microfilarial skin densities (MFD) observed in 1987 and 1992 in 5-7-year-old children who had never taken the drug but who were members of the treated communities. In 1992, the PMF and the MFD in children in this age group who never received ivermectin were reduced by 55% and 77%, respectively, in comparison with the values observed in 1987, before the first treatment round. These results reflect a pronounced reduction in the intensity of the transmission of Onchocerca volvulus in the treatment zone. The influence of the ivermectin treatment coverage in the human population, as well as the vectorial capacity and the dispersal of the vector blackflies, on the transmission of onchocerciasis is discussed.

[The use of ivermectin in the control of onchocerciasis]. / Apport de l'ivermectine dans le contrôle de l'onchocercose.

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.

[Subcutaneous nodules and cutaneous lesions caused by different Onchocerca in African cattle]. / Nodules sous-cutanés et lésions cutanées engendrés par diverses onchocerques chez des bovins africains.

Subcutaneous nodules and skin biopsy specimens obtained from the umbilical area of 6 onchocercal Bos indicus were collected in Cameroon and subjected to a histological examination. The nodules containing Onchocerca ochengi and Onchocerca dukei showed the same structure as Onchocerca volvulus nodules in man; they consisted of inflammatory pseudo-cysts often containing a female filaria. These pseudo-cysts were classified as "young", "active" and "old" depending on the inflammatory cellular component of their walls. The nodules were surrounded by a connective tissue capsule criss-crossed by vessels containing sections of microfilariae and morula in the vascular lumen. The skin, infected with microfilariae of these two species, of O. gutturosa and O. armillata, showed various dermatitis lesions with fibrosis, similar to those observed in patients with onchocerciasis. In most cases, inflammatory infiltrates surrounded the lymphatic capillaries along the blood vessels, giving rise to lymphangitis. The presence of microfilariae inside the granulomatous tissue demonstrates that microfilariae were deposited directly into the cystic lumen. Only the microfilariae which escaped the inflammatory reaction were able to penetrate the lymphatic vessels. They could then migrate into the lymphatic system and reach the superficial layer of the dermis. Bovine nodular onchocercomata represent an interesting model for human onchocerciasis.

Density-dependent processes in the transmission of human onchocerciasis: intensity of microfilariae in the skin and their uptake by the simuliid host.

The transmission success of Onchocerca volvulus is thought to be influenced by a variety of regulatory or density-dependent processes that act at various points in the two-host life-cycle. This paper examines one component of the life-cycle, namely, the ingestion of microfilariae by the simuliid vector, to assess the relationship between intake of larvae and the density of parasites in the skin of the human host. Analysis is based on data from three areas in which onchocerciasis is endemic and includes published information as well as new data collected in field studies. The three areas are: Guatemala (Simulium ochraceum s.l.), West and Central Africa (savanna members of the S. damnosum complex), and South Venezuela (S. guianense). The data record experimental studies of parasite uptake by flies captured in the field and fed to repletion on locally infected subjects who harboured varying intensities of dermal microfilarial infection. Regression analyses of log transformed counts of parasite burdens ingested by the flies plotted against log transformed counts of microfilariae per mg of skin revealed little evidence for saturation in parasite uptake by the flies as the intensity in the human host increased. There was a positive and highly significant rank correlation between both variables for the three blackfly species. In an alternative analysis a model was fitted to data on prevalence of flies with ingested microfilariae (mff) versus dermal mean intensities. The model assumed an overdispersed distribution of the number of mff/fly and a given functional relationship between intake and skin load. The results of both approaches were consistent. It is concluded that parasite ingestion by the vector host is not strongly density dependent in the three geographical areas and ranges of dermal loads examined. It therefore appears that this transmission process is of reduced importance as a regulatory mechanism in the dynamics of parasite population growth.

[Long-term effect of a single dose of ivermectin on skin microfilarial density in an endemic onchocerciasis area of North Cameroon]. / Effet à long terme d'une prise unique d'ivermectine sur les charges microfilariennes dermiques dans un foyer d'onchocercose du Nord-Cameroun.

The long-term efficacy of a single dose of ivermectin (150 micrograms/kg) on skin microfilarial densities was evaluated by comparing parasite levels, before and after treatment, in 192 patients living in an area endemic for onchocerciasis in North Cameroon. A mass treatment with ivermectin has been undertaken in 1989 in two villages, where pretreatment community microfilarial loads (CMFL) were 5.5 and 25.1 microfilariae per snip. The parasitological examination carried out 32 months later showed that the microfilarial densities in the adults where only 24 and 51% of the initial values, respectively. In a third village, treated once in 1989 but located in an area where annual mass distributions of ivermectin have been undertaken since 1987, the mean microfilarial density 28 months after treatment was only 12% of the initial value. In 1992, the mean microfilarial load in children had decreased significantly in comparison with those of 1989 only in the village where the level of endemicity was initially the lowest. The rate of increase in the number of skin microfilariae after one dose of ivermectin is related with the pretreatment endemicity level. The impact of large-scale ivermectin treatments on the transmission of onchocerciasis enhances the long-term efficacy of this drug on the skin microfilarial densities.

[Parasitological efficacy of repeated treatments with ivermectin in an onchocerciasis focus in north Cameroon]. / Efficacité parasitologique de traitements répétés par l'ivermectine dans un foyer d'onchocercose du Nord-Cameroun.

321 adults living in an hyperendemic onchocerciasis focus in North-Cameroon who received a first dose of ivermectin (150 micrograms/kg) in 1987 and a total of three, four or five doses from 1987 to 1991 were parasitologically examined in 1992. The prevalence of skin microfilariae (PMf) and the geometric mean microfilarial load (GMMf) were respectively reduced by 33 and 97% from the initial values in the group of subjects who received five treatments. In 1992, the PMf and the GMMf were not significantly different in the groups which received three, four or five doses of ivermectin. It is not necessary to achieve an important drug coverage to maintain a tolerable level of infestation in the community.

[Control of onchocerciasis with ivermectin: results of a mass campaign in northern Cameroon]. / Lutte contre l'onchocercose par ivermectine: résultats d'une campagne de masse au Nord-Cameroun.

A mass chemotherapy campaign to treat onchocerciasis with ivermectin was carried out in northern Cameroon, in the North Vina valley, a savanna area that is part of the extended Vina-Pendé-Longone focus. More than 20,000 people aged five years and over were treated at least once and more than 30,000 treatments were distributed. One to four treatments were given at intervals of six months or one year. Clinical and parasitological examinations of representative samples of the treated population and full ophthalmological examinations of males aged 15 to 35 years were carried out before each treatment to assess the efficacy of the different protocols of treatment. Secondary effects were recorded daily during the week after administration of ivermectin in the whole population treated. The evolution of arterial blood pressure was monitored over seven days in about 300 adults living in the hyperendemic region. The impact of mass treatment on natural transmission of the disease was evaluated by daily capture and dissection of blackflies during the month before and the two months after treatment. All levels of onchocerciasis endemicity were represented in the study area (maximum community microfilarial load (CMFL), 300 microfilariae per biopsy). Six months and one year after the first treatment, loads were down by more than 90% and more than 60% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Parasitology in France: some aspects of the present.

Numerous organizations participate and cooperate on parasitological research in France including the Institut national de la Santé et de la Recherche Médicale (INSERM), the Centre national de la Recherche Scientifique (CNRS), the Institut Pasteur, the Institut Français de Recherche Scientifique pour le Développement en Coopération (ORSTOMM), the Institut national de la Recherche Agronomique (INRA), the Muséum national d'Histoire naturelle (MNHN), the Universities, the Collège de France, the Ecole Pratique des Hautes Etudes (EPHE) as well as various commercial firms. Exchanges and collaborations with foreign workers are continuous and essential to the success of research on tropical diseases. Here, in their own words, Odile Bain, Daniel Camus and Jacques Prod'hon highlight some aspects of current parasitological research in France.

Forest and savanna onchocerciasis: comparative morphometric histopathology of skin lesions.

A comparative study was made of skin biopsies from onchocerciasis patients living in the forest and in the savanna of West Africa. The lesions and their pathogenesis were similar in the two series of patients. An inflammatory reaction around the extra-lymphatic microfilariae was observed. But the localization of the microfilariae was slightly different: the mean distances between the microfilariae and the border of the basement membrane of the epidermis was approximately 115 microns in the forest and 138 microns in the savanna. Statistical analysis showed that the forest microfilariae were in the superficial parts of the dermis when the densities were low and in deep parts of the dermis when the densities were high. In the savanna, the phenomenon, although less clearly defined was reverse. The two situations were inverted when the density of microfilariae reached approximately 51 microfilariae per calibrated snip, which was seldom the case. Therefore, the most cases, microfilariae appeared to have been more superficial in the forest than the savanna.

Characterization of an immunodominant Onchocerca volvulus antigen with patient sera and a monoclonal antibody.

Adult Onchocerca voluvlus and infective larvae, but not microfilariae contain an immunodominant antigen (33,000 and 21,000 Mr in females, 39,000, 33,000, and 21,000 Mr in males, 133,000 Mr in infective larvae) which is recognized by an Onchocerca-specific mAb. The component is part of the reproductive organs and muscles. 96.2% of onchocerciasis sera contained antibodies detectable by immunoblotting against it. Antigen purified by immunoaffinity chromatography was specifically recognized in immunoblots by onchocerciasis sera, but not by sera from other filarial infections. The high immunogenicity, the specificity, and the occurrence in infective larvae of this antigen indicate an immunodiagnostic potential and a possible role in the immunobiology of the parasite.

Antibody responses in forest and savanna onchocerciasis in Ivory Coast.

Three foci of onchocerciasis transmission (two forest and one savanna, respectively) in the Republic of Ivory Coast were chosen for a comparative analysis of Onchocerca volvulus antigens and of patients' antibody responses. Clear differences between frequency and intensity of ocular pathology existed between the forest foci and the savanna focus. We found heterogeneity of SDS-PAGE-separated components of female worms with respect to the mobility of three protein bands of the 100 KD region and to the ability of an 80 KD band to bind horseradish peroxidase. These variations were clearly not associated with the degree of ocular pathology. No differences in the composition of worm antigens were detected by immunoblotting. A variable with a possible relation to ocular pathology was the antibody response of patients: individuals from the savanna focus, where a high degree of ocular pathology is observed, tended to have a stronger and more differentiated IgG antibody response against O. volvulus antigens than patients from the forest foci. However, no antigens specifically recognized by patients from either forest or savanna were detected.