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Onchocerciasis: invasion of deep organs by Onchocerca volvulus.

Autopsies of two patients with onchocerciasis in the Republic of Zaïre are reported. In one patient elephantiasis who died following diethylcarbamazine therapy there were large numbers of microfilariae of Onchocerca volvulus in the kidney, liver, pancreas, and lung. In the second patient, who also had leprosy and hyperinfection strongyloidiasis, we found an encapsulated adult O. volvulus in the wall of the thoracic aorta.

Aorta, Thoracic↗

Seasonality of adult black flies and Onchocerca volvulus transmission in Guatemala.

Transmission of Onchocerca volvulus, principally by Simulium ochraceum, was studied over a 14-month period in the Atitlán region of Guatemala. Semimonthly catches of black flies were made on human volunteers at 4 localities with different prevalences of human onchocerciasis. Host-seeking activity of S. ochraceum reached its greatest magnitude in the early dry season (October-January) but then declined rapidly and was lowest during the late dry season (February-May). The frequency of O. volvulus larvae in parous host-seeking S. ochraceum also varied seasonally, and this variation was most pronounced for third stage larvae. At a hyperendemic locality, the highest frequency of this larval stage occurred during the February-March period (0.0142 in 1979 and 0.0095 in 1980). From June-January, the frequency of third stage larvae in S. ochraceum was less than 0.003. The frequency of early first stage larvae exhibited the least seasonal variation, ranging from 0.0354 in August-September to 0.0628 in April-May. The transmission rate of O. volvulus by S. ochraceum also varied seasonally. At the same hyperendemic locality, infective biting density of S. ochraceum attained its greatest magnitude in February-March. The survival rate of female S. ochraceum from one gonotrophic cycle to the next was estimated from the ratio of flies with early first stage larvae to those with infective stage larvae. These rates varied seasonally and ranged from 0.2132 to 0.3974, with the highest rates occurring in the late dry season.

Animals↗

[Variations under genetic control of onchocerca infection as a function of clinical profile in the endemic center of Cameroon].

Onchocerciasis, also known as "river blindness", presents a plenum of clinical manifestations which vary from one individual to another, and from one area to another. This large spectrum of clinical manifestations of the disease is an indication of the complexity of the pathogenesis of onchocerciasis and suggests that many interacting factors might influence the clinical features of the disease. The present study has focused on the heterogenicity of the host immune response as a plausible explanation for differences in clinical manifestations of the infection. Host genetic factors, namely HLA genes, might play an important role in determining the nature of the immune response mounted against the parasite Onchocerca volvulus, and thus the development of different manifestations of the infection. Genetic diversity of onchocerciasis was assessed in different endemic foci in Cameroon. In order to investigate the possibility that the Major Histocompatibility Complex (MHC) genes might be associated with the different clinical types of onchocerciasis, 146 subjects living in three endemic areas of Cameroon were studied. They were classified in four groups: A (asymptomatic subjects), P (putatively immune subjects) L (patients with localised disease) and G (patients with generalised disease). The four groups differed in the distribution of HLA class II alleles as determined by Direct Heteroduplex Analysis. On the one hand, allele HLA-DQA1*0501 appeared to be associated with protection against severe onchocerciasis; on the other, allele HLA-DQB1*0201 might play an important role in the severe form of the disease.

Alleles↗

Onchocerca cervicalis infection in horses from the western United States.

In a study of Onchocerca cervicalis infection in a sample of 100 horses from the western United States, 48 were infected. Infection was more common in older horses and occurred in both sexes equally. Data about the distribution and the concentration of microfilariae within the skin are presented. The only cutaneous pathologic change that could be attributed to microfilariae was minimal perivascular inflammatory cell infiltrate. Invasion of the eye with microfilariae occurred in 60 percent of the infected horses. An attempt was not made to relate microfilarial invasion of the eye with ocular pathologic changes.

Animals↗

Factors influencing the passage of Onchocerca volvulus microfilariae into the urine.

The effect of various substances on the output of Onchocerca volvulus microfilariae in the urine was investigated in volunteers infected with the Cameroon forest and Sudan-savanna strains of the parasite. Output of microfilariae in the urine tended to be higher during periods of normal activity than during sleep. During waking hours, the rate of output remained generally steady, but in some patients occasional showers of microfilariae appeared in the urine, possibly associated with the intake of food and drink. Drinking 1.2-2.5 litres water produced a shower of microfilariae in the urine of some subjects. This began within an hour of drinking and its onset preceeded that of the diuresis. Thiazide diuretics, acting on the convoluted tubules, produced no increase in microfilaruria. In savanna subjects intravenous injection of DT TAB vaccine caused pyrexia, and simultaneously large numbers of microfilariae appeared in the urine. There was no associated diuresis, and no increase in the concentration of microfilariae in the venous blood. In forest subjects DT TAB caused no increase in microfilaruria. In all subjects 25-50 mg diethylcarbamazine (DEC) caused large numbers of microfilariae to appear in the urine on day 0, within a few hours of the first dose; and there was an increased output of urine over the first 24 hours. Microfilaruria declined sharply on day 1 of treatment, but in subjects developing a high microfilaraemia, it rose again on day 2, and declined more slowly thereafter. Betamethazone, given in conjunction with DEC, appeared to slow the rate of destruction of microfilariae in the skin and lymph glands, and to prolong the duration of microfilaraemia and microfilaruria. The findings suggest that there is a reservoir of microfilariae in the glomerular capillaries, which fills slowly by accumulating microfilariae from the circulating blood. The microfilariae probably enter the urine by penetrating the glomerular capillary.

Adult↗

Fundus lesions in the rabbit eye following inoculation of onchocerca volvulus microfilariae into the posterior segment. II. Pathology.

The injection of living microfilariae of Onchocerca volvulus into the vitreous or immediately beneath the retina of rabbits gave rise to a variable degree of choroiditis. Uveal inflammation was most marked in eyes inoculated directly into the retina and subretinal tissue. The choroiditis was characterised by lymphocytic, plasma cell and eosinophil infiltration and was associated in many instances with degeneration of the overlying retina and pigment epithelium. In the eyes of animals killed more than 40 days after inoculation with microfilariae the leucocytic infiltration was usually mild or even absent, and the predominant finding was circumscribed atrophy and degeneration of the retina. It is concluded that the pathogenesis of the lesions in posterior segment onchocerciasis is basically inflammatory with, possibly, a direct toxic action of the microfilariae on the retina.

Animals↗

Fundus lesions in the rabbit eye following inoculation of onchocerca volvulus microfilariae into the posterior segment. I. The clinical picture.

Live microfilariae of the Cameroon forest and Sudan-savanna strains of Onchocerca volvulus were inoculated into the vitreous or into the subretinal layers of the eyes of rabbits. The lesions produced are described, and are compared with those seen in control animals, which had received inocula of microfilariae-free saline supernate introduced with a similar degree of operative trauma. Control rabbits showed only minor pigment disturbance in the retina and choroid, near the healed operation scars. Infected animals showed evidence of an inflammatory process in the eye, lasting for up to 4 weeks. Fundus lesions developed following inoculation of microfilariae into the vitreous, but they were more frequent and more severe following subretinal inoculation. The lesions produced were: pallor, vascular narrowing, and flattening of the optic disc; subretinal inflammatory exudate, giving rise to a disturbance of pigment in the retinal pigment epithelium; scattered, small choroidoretinal scars, and larger circumscribed areas of choroidoretinitis, sometimes accompanied by optic atrophy. In many eyes inoculated with microfilariae the wincing reflex was lost, indicating some visual impairment. Many of the lesions were similar to those seen in human patients with onchocerciasis, but they developed much more rapidly. Microfilariae inoculated intravenously, or into the periocular tissues, were not observed to penetrate into the eye-ball.

Animals↗

Importance of migrants infected with Onchocerca volvulus in west African river valleys protected by 14 to 15 years of Simulium control.

A study was done to determine the importance of human migration from non-controlled endemic onchocerciasis foci to the river valleys that have been protected for the past 14 to 15 years by the vector control operations of the Onchocerciasis Control Programme in West Africa. The aim of the study was to assess the contribution of migrants to the prevalence and intensity of infection in villages from 5 major river valleys and their potential role in causing relapse of transmission once the vector is allowed to return. In Burkina Faso the migrant population varied from 0.0% to 18.1% of the village population, and averaged 4.9%. Migrants accounted only for 0.6% of the population in Ghanaian and Ivorian villages along the Black Volta river. The prevalence of infection was significantly higher in migrants (8.2%) than in non migrants (1.1%) in the surveyed villages in Burkina Faso, and 1.5% of migrants had infections with more than 16 microfilariae per snip as against 0.2% of non migrants. Nearly all infected migrants came from the south of the Côte d'Ivoire. The study shows that human migration has caused the importation of Onchocerca volvulus from non-controlled areas. However, the epidemiological importance of this phenomenon is limited because of the very small number of infected migrants per village while two-third of the infected migrants are believed to be infected with the less pathogenic forest strain of the parasite. Because migration patterns changes geographically and over time similar studies will be continued on a regular basis.

Animals↗

Viability of adult Onchocerca volvulus after six 2-weekly doses of ivermectin.

Ivermectin is a safe, effective microfilaricide and microfilarial suppressant for Onchocerca volvulus; but in single doses of 100-200 micrograms/kg body weight it has no macrofilaricidal action. The present trial aimed to determine whether 6 doses of 100 micrograms/kg ivermectin, given at 2-week intervals, would kill the adult worms. Eighty-two nodules from 28 otherwise healthy adult male Liberian patients treated with this ivermectin schedule, and 102 nodules from a similar group of 25 control patients, were removed four months after the last dose of ivermectin. They were coded and assessed in a masked fashion either by routine histology or by examination of whole worms extracted from the nodules after collagenase digestion. The drug had no visible effect on adult male worms. More adult female worms were assessed as moribund or dead in the ivermectin-treated group than in the control group (for the collagenase digests P = 0.09; for the histological assessment P = 0.47). The data suggest that repeated dosage with ivermectin may lead to a slow attrition of some female worms and this possibility should be investigated in patients receiving regular doses every 3, 6 or 12 months as part of onchocerciasis control programmes.

Adult↗

Ivermectin uptake and distribution in the plasma and tissue of Sudanese and Mexican patients infected with Onchocerca volvulus.

Ten Sudanese patients with Onchocerca volvulus infection were treated with a single oral dose of 150 micrograms/kg of ivermectin. Plasma samples were collected before treatment, 0.5, 1, 3, 4, 6, 12 hours and 1, 2, 3, 7, and 30 days. Four patients were selected for nodulectomies and skin biopsies at 6, 18 and 30 hours and 3 days post treatment. Using these samples O. volvulus worm fragments were dissected free of host nodular tissues for ivermectin extraction. Ivermectin was present in the nodular tissue at 6 hr and persisted for 3 days. It was also detected in an individual worm tissue extract at a concentration similar to the nodule, but in subcutaneous fascial tissue higher concentrations were sometimes found. Ivermectin was detected by radioimmunoassay in the plasma of all patients at 1 hr and peak concentrations were reached in an average of 5.6 hr. The drug persisted at detectable levels for 7 days in 70% of the studied patients. Plasma samples were also collected from 16 treated Mexican onchocerciasis patients before ivermectin treatment and 4 hr treatment and from six individuals who served as controls. The Mexican patients had concentrations of ivermectin in their plasma similar to those in the Sudanese patients.

Humans↗

Possible transplacental transmission of Onchocerca volvulus.

In a recent epidemiological study on onchocerciasis on the lower Jos Plateau in Nigeria, a 7-month-old baby delivered by a mother suffering from onchocerciasis showed early clinical signs of the disease: pruritus was present all over the body. The infant's skin snip on incubation revealed microfilariae of Onchocerca volvulus. These findings were confirmed 3 months later when the child was re-examined. No onchocercal nodule was found, but pruritus persisted.

Female↗

[Effects of diethylcarbamazine and ivermectin on the mobilization of microfilariae of Onchocerca volvulus].

Microfilaria of Onchocerca volvulus are localized in superficial dermis. However, they are sometimes noticed in the blood and urines, when there is an important infestation. Diethylcarbamazine (DEC) bring on an increase of microfilaria, successively in the blood and after, in the urines. This study of 30 patients, treated in double blind by placebo, DEC and ivermectin, a new molecule with spectacular action on this filariasis, allowed to compare effect of each one on apparition of microfilariae in the blood and urines. Ivermectin bring on very important increase of microfilaremia without microfilaruria, unlike diethylcarbamazine. This establishment bring to discuss very different physiologic mechanisms between them. It should have an incidence on diagnosis and treatment of this dangerous parasite.

Adult↗

Prevalence, intensity and ocular manifestations of Onchocerca volvulus infection in Dimbelenge, Zaire.

In the zone of Dimbelenge (West Kasai region), Zaire we studied the prevalence, intensity and ocular manifestations of Onchocerca volvulus infection. We used the cluster sampling method to draw a sample of 327 people from a total population of 17,870. The prevalence of microfilaria in skin snips was 82.1% in people 20 years of age and older. The Community Microfilarial Load was 3.5. Blindness in 12 of 13 adults (92.3%) was caused by onchocerciasis. The rate of onchocercal blindness in the adult population was 5.1%. Twenty-four percent of adults had retinal changes as a result of onchocercal infection.

Adolescent↗

Onchocerca cervicalis in horses: dermal histopathology.

A histopathological study of ventral midline skin from midwestern U.S. horses with and without onchocerciasis due to Onchocerca cervicalis found perivascular mononuclear dermatitis as the most consistent difference between the two groups. Seasonal variation in parasite numbers or cellular influxes was not observed. Eosinophilic dermatitis was observed in horses with onchocerciasis and dermatitides of unknown etiology.

Animals↗

Factors influencing the ingestion of Onchocerca cervicalis microfilariae by Culicoides variipennis (Diptera: Ceratopogonidae).

Culicoides variipennis were fed under controlled conditions on two ponies that exhibited seasonal changes in Onchocerca cervicalis microfilarial (mf) skin density and skin distribution. The seasonal changes did not radically affect mf ingestion. Flies were fed on the umbilicus of infected ponies by two methods: individual feeding in consecutive order at the same site, or by mass feeding. Linear regression analysis indicated that ingestion of microfilaria was independent of feeding time and engorged weight. In the individual feeding data, there was a trend toward an increased ingestion of mf as the feeding time increased. Mass feeding trials suggest early feedings by C. variipennis may influence mf ingestion rates of flies that feed on subsequent days. Of the 1,104 flies feeding on both ponies over a 2-year period, 220 (20%) ingested mf and 99 (9% of all engorged flies) ingested only one mf.

Animals↗

Efficacy of ivermectin in paste and injectable formulations against microfilariae of Onchocerca cervicalis and resolution of associated dermatitis in horses.

The efficacy of a single dose of ivermectin (0.2 mg/kg), in injectable or paste formulations, against microfilariae of Onchocerca cervicalis and associated skin lesions was evaluated in 20 naturally infected horses during midsummer months in Louisiana. All horses had clinical signs of dermatitis of the ventral midline and/or limbs, shoulders, thorax, and withers. Efficacy was monitored at 21, 42, and 63 days after treatment. Procedures done at these intervals included microfilarial counts of 6-mm skin biopsy specimens of affected ventral midline, grading of gross lesions, and photography and histologic assessment of ventral midline biopsy specimens. Microfilarial numbers were reduced to 0 by 21 days after treatment in all but one horse. Active lesions improved or were resolved completely by 63 days after treatment. Total inflammation, as judged by histologic methods, was reduced in all horses by 63 days after treatment, but there was a residual population of inflammatory cells in all horses. Adverse reactions after treatment were not observed in any of the horses.

Animals↗

Evaluation of drugs against Onchocerca microfiliariae in an inbred mouse model.

The model of Onchocerca lienalis microfilariae (mf) injected into CBA mice has been examined for its application to chemotherapy studies in onchocerciasis. Parasite recoveries following treatment relative to the levels obtained from controls were not significantly affected by suramin, whereas they were reduced by up to 56% with amoscanate, 71% with levamisole, 82% with mebendazole, 82% with diethylcarbamazine (DEC) and 100% with ivermectin. More detailed evaluation of the latter two compounds demonstrated that far greater intrinsic microfilaricidal activity was possessed by ivermectin compared with DEC. Single doses of ivermectin down to 0.2 mg/kg destroyed 83% of the mf within 12 hours and 100% within 5 days. The same dose administered at various times prior to mf injection reduced parasite recoveries by 92% after four days and by 35-40% for up to one month. In contrast, DEC was only effective at doses of 5 X 50 mg/kg or higher, reducing mf levels by an equivalent amount following subcutaneous or intraperitoneal routes of administration. However, it was of limited efficacy when given to mice during the first week after mf injection compared with the third week, when parasite levels in untreated rodents start to decline under a host immune response. DEC treatment during the third week after mf injection resulted in a smaller depression in parasite recoveries from T-cell deprived mice compared with intact animals, but in similar levels of reduction in CBA/H (normal) and CBA/N (B-cell deficient) mice. Depletion of C3 complement levels in mice with cobra venom factor had a negligible effect on drug efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗