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PubMedDate not supplied

A field study of the effect of ivermectin on intestinal helminths in man.

A single stool specimen from each of 904 villagers participating in a placebo-controlled trial of ivermectin for onchocerciasis was examined for intestinal helminths by the formol-ether technique. Ivermectin had a significant effect on Ascaris infection, reducing prevalence and intensity for at least 3 months, but rapid reinfection occurred. There was no significant effect on Trichuris, Necator or Schistosoma mansoni infections. Incidental Strongyloides infections were not seen commonly in this population, but were significantly reduced in the ivermectin-treated group. Regular administration of ivermectin on a mass basis would reduce the prevalence of Ascaris infection and any attendant morbidity. This is a useful additional effect of the drug.

Animals↗
PubMedDate not supplied

A community trial of ivermectin for onchocerciasis in Sierra Leone: clinical and parasitological responses to four doses given at six-monthly intervals.

Clinical and parasitological responses were studied in villagers receiving all 4 doses of treatment, at 6-monthly intervals, in a placebo-controlled community trial of ivermectin for onchocerciasis in Sierra Leone. Skin microfilarial loads were markedly lowered by ivermectin throughout and there were reductions in the severity, but not the prevalence, of skin lesions. Markers of general health and the prevalences of itching, Onchocerca nodules and visual loss were not significantly reduced during the study period. Despite our inability to demonstrate obvious clinical benefit, treatment with ivermectin was well accepted throughout the study. Simple clinical measures for evaluating the short to medium term impact of the mass distribution of ivermectin on populations with onchocerciasis need further development.

Adult↗
PubMedDate not supplied

Long-term suppression of microfilaraemia following ivermectin treatment.

Lymphatic filariasis has been difficult to control until recently because of the lack of a suitable drug for treatment. Ivermectin has proven safe and effective at reducing levels of circulating microfilariae. However, the apparent need to administer the drug every 6 to 9 months to keep microfilaraemia levels sufficiently suppressed to reduce transmission has been a major drawback to using ivermectin in community-based intervention programmes. In a study conducted in Haiti, we have found that high doses of ivermectin suppress microfilaraemia levels for 2 years. Our findings suggest that a single dose of ivermectin can reduce transmission of lymphatic filariasis for extended periods of time, thus eliminating the need for costly biannual treatment.

Adolescent↗
PubMedDate not supplied

Microfilariae recurrence in Polynesian Wuchereria bancrofti carriers treated with repeated single doses of 100 micrograms/kg of ivermectin.

Forty-six Polynesian carriers of Wuchereria bancrofti were treated with 3 successive single doses of ivermectin, 100 micrograms/kg, given every 6 months. Immediate microfilaricidal activity of ivermectin was excellent in all carriers, since residual mean microfilaraemia levels, 2 d after each of the 3 treatments, were less than 1% of pretreatment levels. Before initial treatment, geometric mean microfilaraemia was 500 microfilaria (mf)/ml for the whole group (range 21-6398 mf/ml); 6 months after each successive treatment it was 197, 108 and 87 mg/ml, respectively, 39.4, 21.6 and 17.4% of the pre-initial treatment level. By considering the mean percentage recurrent level at 6 months after the 3rd treatment (36.8%) as a threshold, it was possible to classify the carriers into 2 groups: 17 in whom the percentage recurrent level was > 36.8% and who were considered as 'fast repopulating' individuals, and the remaining 29 who were considered as 'slow repopulating' individuals. In the latter group, 6 months after each of the 3 treatments, the recurrent microfilaremia levels were 22.7%, 8.0% and 4.9% of the pre-initial treatment level, respectively, while they were 95.1%, > 100% and > 100% in the former. The constant recurrence of mf suggests that ivermectin, at a dosage of 100 micrograms/kg, had no effect on adult worms in 'fast repopulating' individuals, whereas the progressive lessening in recurrence of mf suggests some activity (sterilizing or killing) of ivermectin on W. bancrofti macrofilariae in 'slow repopulating' individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Efficacy of ivermectin in the treatment of concomitant Mansonella perstans infections in onchocerciasis patients.

As part of an ivermectin dose-ranging study of onchocerciasis patients in Togo, 55 onchocerciasis patients with concomitant mansonelliasis received single oral doses either of ivermectin (100 to 200 micrograms/kg body weight) or placebo. As expected, Onchocerca volvulus microfilariae in the skin were greatly reduced in number soon after drug treatment, but microfilariae of Mansonella perstans reacted differently. Microfilarial densities of M. perstans were assessed with a filtration technique both before, and 4 times after, treatment. In untreated patients microfilarial densities were stable until the end of the study at 6 months. In patients receiving ivermectin, microfilarial densities dropped on average to less than 60% of the pre-treatment level and remained there until the final post-treatment examination. This partial reduction was probably not caused by a microfilaricidal effect of ivermectin, but rather by an altered distribution of microfilariae in the peripheral blood and in a suspected microfilarial reservoir.

Animals↗
PubMedDate not supplied

Lack of effect of ivermectin on prepatent guinea-worm: a single-blind, placebo-controlled trial.

The effect of ivermectin on prepatent guinea-worm was tested in a single-blind placebo-controlled trial; 400 adults were randomly allocated to a single dose of ivermectin (150 micrograms/kg) or placebo. Fifty-four of the 385 participants who were followed for 15 months developed a total of 69 emergent guinea-worms. There was no significant difference in the proportion of persons with emergent guinea-worms between the 2 treatment groups; 58% appeared in males. 80% of emergent guinea-worms were located below the knee. Migration of guinea-worms in the tissues was not affected. It is concluded that ivermectin has no effect on prepatent guinea-worms nor does it disturb their migration pattern. No adverse reaction to treatment was seen. It appears that ivermectin can be used safely as mass chemotherapy against onchocerciasis and lymphatic filariasis in areas where guinea-worm is also endemic.

Adolescent↗
PubMedDate not supplied

Ivermectin 400 micrograms/kg: long-term suppression of microfilariae in Bancroftian filariasis.

Forty-three Wuchereria bancrofti carriers were given 4 successive semi-annual single doses of ivermectin 100 micrograms/kg (IVER 100). The geometric mean microfilaremia (mf) recurrence percentages, compared to the pre-initial treatment mf level, were 35%, 21%, 17% and 17% at 6, 12, 18 and 24 months respectively. However, the recurrence of mf 6 months after the fourth treatment remained high in 15 individuals, considered as 'bad responders'. At month 24, the subjects were randomly allocated into 2 groups: the first group was treated with a fifth dose of IVER 100 and the second with a first, single dose of 400 micrograms/kg of ivermectin (IVER 400). At month 30, the mf recurrence percentage was significantly higher in patients treated with IVER 100 than in those receiving IVER 400 (61% vs. 8%, P < 0.05). In the IVER 100 group, 6 of the 8 'bad responders' remained 'bad responders', whereas only 2 of 7 did so in the IVER 400 group. Only 3 additional patients in the IVER 100 group became consistently amicrofilaraemic, whereas 9 did so in the IVER 400 group. Two 'good responders' in the IVER 100 group became 'bad responders'. A single dose of 400 micrograms/kg of ivermectin has been demonstrated to be efficient for the treatment of carriers refractory to repeated doses of 100 micrograms/kg and to result in better long-term mf suppression. These results suggest a possible effect of 400 micrograms/kg of ivermectin on macrofilaria.

Adolescent↗
PubMedDate not supplied

Direct assessment of the adulticidal efficacy of a single dose of ivermectin in bancroftian filariasis.

Although the potent microfilaricidal activity of ivermectin is well established, its efficacy against adult Wuchereria bancrofti is unknown. We used longitudinal ultrasound examinations for periods of 3-9 months to assess directly the macrofilaricidal effect of a single 400 micrograms/kg dose of ivermectin in 15 men from Recife, Brazil who were infected with W. bancrofti. Before treatment, microfilarial densities ranged from 3 to 3098 microfilariae per mL of blood, and movements characteristic of the living adult worm (the 'filaria dance sign') were observed by ultrasound examination of the scrotal lymphatic vessels in all 15 men. Following treatment, microfilarial density was markedly reduced in all men, but the filaria dance sign remained unchanged in both location and pattern. Eight months after treatment, a dilated lymphatic vessel was surgically removed from one patient at the site of the filaria dance sign, and 3 intact adult worms were released. When given as a single 400 micrograms/kg dose, ivermectin had no observable effect on adult W. bancrofti. Therefore, prolonged suppression of microfilaraemia following treatment with ivermectin cannot be explained by a macrofilaricidal effect of the drug. Ultrasound is a valuable new tool for directly and rapidly assessing the macrofilaricidal efficacy of antifilarial drugs in lymphatic filariasis.

Adult↗
PubMedDate not supplied

Low level ivermectin coverage and the transmission of onchocerciasis.

Regular collections of biting Simulium damnosum s.l. were carried out during a community-based trial of doses of ivermectin every 6 months for onchocerciasis in Sierra Leone. Over 64,000 blackflies were caught at 4 sites close to treated villages and one site near an untreated village. More than 17,000 of these blackflies were dissected during the 31 months of the study and 5 doses of ivermectin were distributed to about 30% of the human population in the treated villages. High annual biting rates (about 100,000 bites per year) and transmission potentials (about 5000 larvae per year) were found at all catching sites. Approximately 30% of parous blackflies carried Onchocerca volvulus larvae, and 8% had infective stage larvae. None of these indices appeared to be affected by the distribution of ivermectin. However, the mean number of larvae per infected blackfly fell from 8.7 to 5.8 during the study period in the treated villages, equivalent to a 21% decrease per year. No such reduction was seen in the control village. This study demonstrates that in areas where high capacity vectors predominate, the effect on transmission of even a low coverage of the human population with repeated doses of ivermectin may be detectable using the sensitive entomological index of intensity of infection in infected flies. Statistical analysis of onchocerciasis transmission data is a complex issue and ways of improving the design of trials and applying appropriate statistical methods are discussed.

Animals↗
PubMedDate not supplied

Ivermectin treatment in severe asymmetric reactive onchodermatitis (sowda) in Sudan.

Ivermectin efficacy and post-treatment reactions in asymmetric severe reactive ochodermatitis (sowda) were studied in 8 patients with sowda syndrome and 6 with mild generalized onchodermatitis in Sudan. Initial skin snips from 12 patients contained microfilariae (1-9 per mg skin). Patients were treated in hospital with a single oral dose of c. 150 micrograms/kg ivermectin (103-200 micrograms/kg) and monitored for frequency and severity of post-treatment reactions for 4 weeks. Serial samples of heparinized blood were collected over the first 24 h after treatment for determination of ivermectin pharmacokinetics. Skin snips from all patients on days 3 and 28 revealed no microfilariae. Post-treatment reactions were more common and severe in individuals with sowda; they consisted mainly of musculoskeletal pain, local swellings with pitting oedema, and lymph gland tenderness and enlargement. No relation was established between these reactions, the microfilarial infection intensity, or the plasma pharmacokinetic profiles. A single oral dose of ivermectin cleared the skin of microfilariae and led to improvement of symptoms and dermatological signs of sowda, but resulted in more marked reactions than in cases of generalized onchodermatitis.

Adolescent↗
PubMed1990

Safety of and compliance with community-based ivermectin therapy.

In a study of the safety, acceptability, and efficacy of ivermectin for community-based mass treatment of onchocerciasis, the drug was issued twice, one year apart, to the population of a rubber plantation (14,000 people) in Liberia, where over 80% of the adults have Onchocerca volvulus infection. The plantation microfilarial load in a sample of adults was reduced by 86% 6 months after initial treatment and by 78% after 1 year. Compliance was 97% with each round of treatment. After the initial treatment of 7699 people, 101 (1.3%) had moderate adverse reactions. After re-treatment only 37 (0.5%) people had moderate adverse reactions. No ivermectin-related death or severe adverse reactions occurred. The data show that community-based treatment with ivermectin is well accepted and effective in reducing microfilarial loads. Ivermectin is likely to provide the first realistic means of chemotherapy-based control of onchocerciasis on a mass scale.

Adolescent↗
PubMed1992

Ivermectin: its effect on the immune system of rabbits and rats infested with ectoparasites.

The influence of subcutaneously administered ivermectin on the specific immune response was studied in rabbits infested with mites (Psoroptes cuniculi) and in rats infested with lice (Polyplax spinulosa). A pronounced specific antibody activity and a change in immunoblotting pattern was observed in rabbits after the ivermectin treatment. However, in rats the antibody activity decreased and the profile of specific antibodies, tested by immunoblotting, remained the same as before the treatment. The specific immune response in rabbits artificially immunized with whole-body Psoroptes cuniculi extract was not affected by ivermectin. It was concluded that ivermectin has no direct effect on the immune response of rabbits and rats and that the enhanced immune response in the mite-infested rabbits was caused by the massive release of antigens associated with the synchronous death of the mites.

Animals↗
PubMed1995

Influence of ivermectin on cellular and humoral immune responses of lambs.

In view of the extensive use of anthelmintics in sheep and the fact that their activity may in part depend upon the immune system, we were interested to determine if ivermectin had any influence on aspects of the sheep immune response. Ten parasite-free 6-month-old lambs were drenched with ivermectin and 1 day later were given intravenously human erythrocytes and subcutaneously ovalbumin. Ten other lambs with injected antigens were not drenched and served as controls. Both groups were bled at intervals for cells and serum. The procedure was repeated on day 28. Lymphocytes from the drenched lambs, cultured in vitro in RPMI plus 50% autologous serum collected up to 7 and 14 days after the first and second antigen injections respectively, had decreased blastogenic activity compared with lymphocytes from control lambs. Similar results were obtained with lymphocytes cultured in RPMI 1640 supplemented with 50% autologous serum plus concanavalin A (Con A) or phytohaemagglutinin (PHA). When washed, lymphocytes were cultured in RPMI 1640 supplemented with 5% foetal calf serum (FCS) or 5% FCS plus Con A or PHA, decreased blastogenesis was observed but blastogenesis depression was not as marked as that observed with autologous serum. Similar antibody responses were seen for the drenched and control groups in response to the two injections of both antigens except that after the second injection, there was a significant reduction in antibody response to ovalbumin in the ivermectin-treated lambs. There were no differences in serum complement or serum nitric oxide levels between the two groups at any stage, but insulin-like growth factor-1 levels were significantly reduced in serum of the ivermectin-treated group, 4 days after each drench. Growth hormone levels were consistently significantly higher 22 days after both drenchings. There was no difference in mean body weight increase between the groups during the experiment.

Animals↗
PubMed1986

Prophylaxis of nematode infections in cattle with an indwelling rumino-reticular ivermectin sustained release bolus.

Ivermectin delivered continuously from a rumino-reticular sustained release device was prophylactically effective in preventing establishment of nine nematode parasite species in multiply-exposed cattle. Ivermectin dosages which permitted less than or equal to 1% of infected control calf worm populations to establish ranged from less than 2.5 micrograms kg-1 day-1, which totally prevented infection with Dictyocaulus viviparus and Oesophagostomum radiatum, to approximately equal to 30 micrograms kg-1 day-1 required to suppress Nematodirus helvetianus to the same extent. Between these extremes, in decreasing order of sensitivity to enterical sustained release ivermectin, were Ostertagia ostertagi, Trichostrongylus axei, Haemonchus placei, Cooperia punctata, C. oncophora and T. colubriformis which were maximally affected at less than or equal to 10 micrograms kg-1 day-1 of ivermectin.

Animals↗
PubMed1988

The prophylactic effect of ivermectin treatments on gastrointestinal helminthiasis of calves turned out early on pasture or late on mown pasture.

A study was undertaken to ascertain the prophylactic effect on gastrointestinal helminthiasis of (1) a single ivermectin treatment of calves 3 weeks after a late turnout on mown pasture and (2) two ivermectin treatments of calves 3 and 8 weeks after an early turnout. The single ivermectin treatment after a late turnout on mown pasture appeared to be an effective control measure for infections of Cooperia and, in particular, Ostertagia. The two treatments after an early turnout were also effective, although less so than the single treatment combined with the late turnout on mown pasture. Ivermectin treatment had no effect on the faecal egg output or the pasture larval counts of Nematodirus helvetianus. The proportion of inhibited early fourth stage larvae of Ostertagia was much higher in the control group than in either of the experimental groups.

Animals↗
PubMed1989

Factors affecting the efficacy of ivermectin against Heligmosomoides polygyrus (Nematospiroides dubius) in mice.

The efficacy of ivermectin against Heligmosomoides polygyrus was investigated in 5 mouse strains (CFLP, NIH, C57Bl10, BALB/c and CBA) using a variety of dose levels, and subcutaneous and oral administration. Heligmosomoides polygyrus were not completely eliminated when 5 mg kg-1 of ivermectin was given 6 days after infection, but 10 mg kg-1 was totally effective. Significant mouse-strain variation in drug efficacy was detected, NIH mice requiring treatment with higher doses than CFLP mice in order to bring about a comparable level of larvicidal activity. Ivermectin was more effective when given subcutaneously than when given orally, regardless of the dose administered or the strain of mouse tested. The anthelmintic effect of the treatment was more persistent in CFLP mice given 20 mg kg-1 subcutaneously than in NIH mice or in mice treated orally, and a 20-day interval between administration and infection was insufficient to prevent inhibition of parasite survival. Ivermectin was shown to be totally effective at 20 mg kg-1 given subcutaneously in killing immune arrested larvae of H. polygyrus.

Administration, Oral↗
PubMed1989

Comparative study of early-season prophylaxis using ivermectin with lungworm vaccination in the control of parasitic bronchitis and gastroenteritis in cattle.

Twenty-four first-season calves were randomly allocated to three similar groups (1-non-treated controls; 2 - vaccinated against lungworm; 3 - treated with ivermectin 21, 56 and 91 days after turnout) and set-stocked on separate pastures. Parasitic bronchitis became evident in the controls and signs of parasitic gastroenteritis were seen later in the vaccinates, but the ivermectin-treated calves remained healthy. After autumn housing, all were kept as a single group for the winter. The following summer, six of the ivermectin-treated animals and their matching vaccinates were grazed together, without further prophylaxis, along with six first-season calves. The latter displayed evidence of mild but debilitating pulmonary and gastrointestinal parasitic disease while both groups of yearlings remained healthy (with the exception of one diarrhoeic vaccinate). Thus, the immune status of the ivermectin-treated animals appeared to be comparable to that of the vaccinates. This conclusion was supported by parasitological observations and by artificial challenge at the end of the second grazing season.

Animals↗
PubMed1990

Efficacy of ivermectin delivered from an intraruminal sustained-release bolus against natural infestations of five African tick species on cattle.

The efficacy of ivermectin delivered by an orally administered prototype sustained-release bolus over approximately 90 days was evaluated against natural infestations of five African tick species. Twenty cattle, allocated by restricted randomization based on counts of standard Boophilus decoloratus, were allocated to two groups and were either given an ivermectin bolus or designated as non-medicated controls. All cattle grazed a single pasture of native grasses for 20-40 days before treatment and until trial termination. Starting on Days 27, 40, 68 and 82 after bolus administration, four replicates were confined to individual tick-collection stanchions for 4 to 5-day periods. Ticks recovered from these cattle were counted by species, sex, and stage and degree of repletion; engorged females were weighed and incubated to determine the number which oviposited. For the other replicates, half-body counts of adult ticks (classified by species, sex and degree of repletion by females) were made at 1- and 2-week intervals through Day 90. Among replicates confined to stanchions periodically, fewer (P less than 0.05) engorged adult female B. decoloratus, Hyalomma spp., Rhipicephalus appendiculatus and Rhipicephalus evertsi evertsi were collected from bolus-treated cattle than from controls. Numbers of engorged adult female Amblyomma hebraeum were reduced, but differences were not statistically significant (P greater than 0.10). Among cattle maintained continuously on pasture, tick numbers were reduced on the ivermectin-treated groups. A significant (P less than 0.05) treatment by linear time effect was seen for all adult ticks counted except R. appendiculatus. A significant (P less than 0.05) treatment by quadratic time effect was seen for A. hebraeum, B. decoloratus and R. evertsi evertsi, and overall treatment differences were significantly different (P less than 0.05) for these species. The differences tended to increase with time. Except for Boophilus, reductions in tick numbers on treated animals relative to controls were not readily apparent. There were no adverse reactions attributable to ivermectin treatment or the presence of the bolus. Each treated animal retained its bolus throughout the trial, based on metal detection.

Administration, Oral↗