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PubMed1990

Comparison of a levamisole sustained-release bolus and ivermectin treatment to prevent bovine lungworm infection.

The efficacy of a levamisole sustained-release bolus to prevent parasitic bronchitis in calves in their first grazing season was compared to ivermectin treatment at three, eight and thirteen weeks after turn out. Contamination of the pasture was established by experimentally infected seeder calves. Twenty calves were split into two groups. Ten calves of one group received a bolus at the start of the experiment. In the other group the calves were treated with ivermectin at 21, 56 and 91 days. Two principal calves from each group were killed during the experiment to study histopathological changes. Pairs of tracer calves were introduced on both pastures at intervals of four weeks throughout the grazing period. The permanent calves were challenged with lungworm larvae at housing and slaughtered four weeks later. Both systems prevented parasitic bronchitis. Larval output was completely reduced in the ivermectin-treated calves while all bolus-treated calves excreted larvae at certain times. The highest group average was 4 larvae per gram faeces. Eosinophilia, ELISA-titres and histopathological changes confirmed the differences in larval uptake. Challenge infection was not successful in either group and no worms were found at slaughter. Weight gain was significantly different at housing in favour of the ivermectin-treated calves, but after challenge this was reduced due to a higher weight gain in the bolus-treated calves. The practical consequences of the results have been discussed.

Animals↗
PubMedDate not supplied

Ivermectin residues in the edible tissues of swine and cattle: effect of cooking and toxicological evaluation.

Young male pigs (25-40 kg bw) were treated experimentally with a single 0.4 mg/kg bw, s.c. dose of ivermectin (Ivomec vet. inj., MSD). The disappearance of the drug from the edible tissues 7-21 days after treatment was studied using a sensitive high-performance liquid chromatographic method. The highest residue levels were found at the injection site (up to 59 and 2.6 mg/kg 7 and 14 days post-injection, respectively). Among the other tissues studied, the residue levels 7 days post-injection showed the following order: liver (less than or equal to 50 micrograms/kg) greater than kidney (less than or equal to 25 micrograms/kg) greater than muscle (less than or equal to 20 micrograms/kg). After 21 days only traces of ivermectin (less than or equal to 2 micrograms/kg) could be detected in the muscle and other edible tissues, including the injection site. Similar residue concentrations were found in slaughterhouse material from sows therapeutically treated with ivermectin for parasite infestation. An ordinary culinary preparation of the minced beef muscle from a bull treated with ivermectin resulted in a 45% (boiling) or 50% (frying) decrease in the drug residue. Based on the known toxic effects of the drug and the results of the present and other residue studies, the suggested withdrawal time for Ivomec in edible tissues of swine and cattle is 21 and 28 days, respectively.

Animals↗
PubMed2005

Oral ivermectin for the treatment and prophylaxis of scabies in prison.

INTRODUCTION: Oral ivermectin has been widely used to treat various human diseases, such as filariasis, myiasis, larva migrans, strongyloidiasis and scabies (both the common and crusted forms). However, there are only a small number of papers on the effects of this drug for the control of scabies in infested environments. The current study shows the results obtained with the collective treatment of inmates of a public jail. MATERIALS AND METHODS: A total of 123 inmates living in a restricted and contaminated environment were evaluated clinically by experienced dermatologists for the assessment of the degree of infestation by Sarcoptes scabiei, and were then treated with oral ivermectin (200-300 micorg/kg single dose repeated after 7 days). Both clothing and environment were disinfected. Patients were re-evaluated after 15 days. RESULTS: In all, 78% of the inmates were infected upon initial evaluation. Re-evaluation 15 days after repeat treatment revealed a cure rate of 91.05%. Prophylaxis was also highly effective, where 93.2% of the non-infected inmates and virtually all the house staff remained disease-free throughout the study period. Two of the 29 inmates (6.8%) who showed no apparent lesions upon initial examination were found to be infected upon re-evaluation. These patients responded well to a third dose of ivermectin. CONCLUSIONS: Oral ivermectin at a dose of 300 microg/kg single dose repeated after 7 days proved effective for the treatment and prophylaxis of scabies in an infected institutional environment.

Administration, Oral↗
PubMed2000

Cutaneous larva migrans in travelers: a prospective study, with assessment of therapy with ivermectin.

The purpose of this prospective study was to update epidemiological data on cutaneous larva migrans (CLM) and to assess the therapeutic efficacy of ivermectin. We performed the study between June 1994 and December 1998 at our travel clinic. Ivermectin (a single dose of 200 microg/kg) was offered to all the patients with CLM, and its efficacy and tolerability were assessed by a questionnaire. Sixty-four patients were enrolled. All were European and had stayed in tropical areas. After the patients had returned from their destinations, 55% had lesions occur within a mean of 16 days (range, 1-120 days; >1 month in 7 patients). The initial diagnosis was wrong in 55% of patients. The mean number of lesions was 3 (range, 1-15), and the main sites were the feet (48%) and buttocks (23%). The cure rate after a single dose of ivermectin was 77%. In 14 patients, 1 or 2 supplementary doses were necessary, and the overall cure rate was 97%. The median time required for pruritus and lesions to disappear was 3 and 7 days, respectively. No systemic adverse effects were reported. Physicians' knowledge of CLM, which can have a long incubation period, is poor. Single-dose ivermectin therapy appears to be effective and well tolerated, even if several treatments are sometimes necessary.

Adolescent↗
PubMed1999

Eosinophil sequestration and activation are associated with the onset and severity of systemic adverse reactions following the treatment of onchocerciasis with ivermectin.

To investigate the role of eosinophil activation and sequestration in the development and severity of adverse reactions after the treatment of Onchocerca volvulus infection, 40 O. volvulus-infected Ghanaians were randomized to receive placebo or standard- or high-dose ivermectin. Subjects were examined for typical physiologic and clinical events before and up to 48 h after treatment. Plasma samples were tested for interleukin (IL)-5 and eosinophil degranulation products (e.g., eosinophil-derived neurotoxin, EDN). After treatment, peripheral eosinophil counts declined in ivermectin-treated groups (P<.001), whereas circulating levels of IL-5 (P<.01) and EDN (P<.05) increased. Cumulative levels of IL-5 and EDN correlated with reaction scores (P<.01). High-dose ivermectin was associated with more-severe reactions, more-profound eosinopenia, and higher circulating levels of IL-5 and EDN, compared with the standard dose. These results suggest that eosinophil sequestration and activation/degranulation are associated with the initiation and severity of ivermectin-associated adverse reactions.

Agranulocytosis↗
PubMed2003

Mechanosensory inputs influence Caenorhabditis elegans pharyngeal activity via ivermectin sensitivity genes.

Mechanical stimulation induces opposite behavioral responses in the adult and dauer pharynx. Tail tap of adults inhibits pharyngeal pumping via a pathway involving the innexin gene unc-7 and components of the glutamatergic pathway encoded by the genes avr-14 and avr-15. Tail tap of dauers stimulates pumping through a mechanism involving G alpha o and G alpha q. The nematocidal drug ivermectin is believed to kill worms by opening a glutamate-gated chloride channel (AVR-15) on pharyngeal muscle, causing complete pumping inhibition. However, ivermectin can also inhibit pumping in the absence of this channel. We propose that one of the ways ivermectin could prevent pumping, in the absence of the AVR-15 ivermectin-binding channel on pharynx muscle, is to target AVR-14 and AVR-15, which are expressed in the inhibitory pathway linking mechanosensation and pumping activity.

Animals↗
PubMed1991

Immunologic responses to repeated ivermectin treatment in patients with onchocerciasis.

To assess the effect of ivermectin treatment on the immunologic status of individuals with onchocerciasis, 27 patients from Guatemala were studied before and at 6-month intervals during 2 years of repeated semiannual treatment with ivermectin. T cell proliferative responses to onchocercal antigen increased transiently by 6 months (mean stimulation index [SI] rising from 4.17 to 12.81) but returned to preivermectin levels thereafter. Changes in SI to nonparasite antigen paralleled those induced by parasite antigen. There were also significant decreases in levels of blood eosinophils, polyclonal IgG and IgE, parasite-specific IgG antibody, and IgG subclass antibodies by the end of the study. This study emphasizes the apparent long-term safety of ivermectin by demonstrating the absence of immunopathogenic responses induced by repeated ivermectin treatments.

Adolescent↗
PubMed1994

Transient changes in cytokine profiles following ivermectin treatment of onchocerciasis.

Cytokine production by peripheral blood mononuclear cells after antigen or mitogen stimulation was assessed before and after semiannual ivermectin treatment of 27 patients with onchocerciasis. Before treatment, Onchocerca volvulus antigen (OvA) elicited interleukin (IL)-5 production but inhibited production of IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha. Six months after the first dose of ivermectin, there were increases in the IL-2, IL-4, IL-5, and interferon-gamma responses to mitogen and in the GM-CSF and IL-10 responses to OvA. By 24 months (after four ivermectin doses), OvA-induced GM-CSF production and mitogen-induced IL-2 and IL-10 production remained elevated above pretreatment levels, whereas that of other cytokines returned to or below pretreatment levels. These transient changes in cytokine response profiles of patients with onchocerciasis following ivermectin treatment likely reflect changes in antigen load.

Adult↗
PubMed1997

Reduction of Wuchereria bancrofti adult worm circulating antigen after annual treatments of diethylcarbamazine combined with ivermectin in French Polynesia.

Circulating filarial antigen (CFA), determined with Og4C3 ELISA, is a marker of Wuchereria bancrofti adult worm infection. The reduction of CFA over 2 years was determined in 185 microfilaremic and 111 amicrofilaremic but CFA+ adults given an annual dose of either diethylcarbamazine (DEC) or ivermectin or the two combined. Reduction of CFA level was good with DEC but weak with ivermectin and followed the same pattern in amicrofilaremic and microfilaremic groups. Combinations and DEC alone had a similar impact on CFA level. CFA clearance was observed in amicrofilaremic but not in microfilaremic persons in all DEC-containing treatments. However, the highest clearance rate was observed in persons treated with DEC at 6 mg/kg combined with ivermectin. Continuous reduction of CFA level after repeated treatments shows that elimination of W. bancrofti infection, monitored by CFA clearance, might be achieved within a few years with annual treatments of DEC combined with ivermectin.

Adult↗
PubMed1998

Delivery of ivermectin by injectable microspheres.

A bioabsorbable, injectable microsphere formulation containing ivermectin in poly-(lactide-co-glycolide) copolymer (PLA/PGA) was developed to provide long-lasting delivery of the drug for control of livestock pests. A solvent-evaporation technique was used to produce the spherical beads containing approximately 30% ivermectin and ranging in size from 25-250 microns. The pattern of delivery of the drug into the blood stream of Spanish goats was characterized for a 50:50 PLA/PGA, a 90:10 PLA/PGA copolymer formulation, and a PLA monomer formulation. When the 50:50 PLA/PGA formulation was used in cattle at the rate of 2 mg (AI)/kg body weight, 2 peaks of 45-50 ppb of ivermectin in serum were observed. The 1st peak was at approximately 1 wk after injection and the 2nd peak, which was broader than the 1st, occurred at approximately 6-7 wk after injection. Percentage of inhibition of estimated larvae for the lone star tick, Amblyomma americanum (L.), placed on treated cattle was 100% for the first 8 wk after injection and was 75, 57, 46 and 44% for wk 9, 10, 11, and 12, respectively. The treatment provided 98-100% control of larval horn flies, Haematobia irritans (L.), in the manure of treated cattle for 10 wk. The bioassay results against lone star ticks and larval horn flies were in agreement with the serum concentration data. The injectable microsphere formulation of ivermectin should be useful in a variety of other applications ranging from the control of Boophilus spp. ticks in south Texas to heartworms in pets.

Animals↗
PubMed2001

Oral ivermectin in scabies patients: a comparison with 1% topical lindane lotion.

Scabies. which constitutes a significant proportion of the outpatient attendance in tropical dermatology clinics, has so far been treated with lindane, crotamiton, sulphur, permethrin, etc. Ivermectin, an orally administered drug, was tried in scabies patients and compared with 1% topical lindane lotion to evaluate its effects and toxicity profile. Two hundred scabies patients were randomly allocated to one of two groups. One group received oral invermectin in a single dose of 200 micrograms/kg body weight. The other received 1% lindane lotion for topical application overnight. Patients were assessed after 48 hours, two weeks and four weeks. After a period of four weeks, 82.6% of the patients in the ivermectin group showed marked improvement; only 44.44% of the patients in the lindance group showed a similar response. A side effects in the form of severe headache were noted in one patient in group A. Oral ivermectin is an easy drug to administer. It is given as a single oral dose, unlike lindane, which has to be applied topically. The compliance is accordingly increased. Moreover, ivermectin induces an early and effective improvement in signs and symptoms. Thus, it may be a better option for scabies than the traditional topical linlane lotion.

Administration, Oral↗
PubMed1992

Ivermectin-facilitated immunity in onchocerciasis. Reversal of lymphocytopenia, cellular anergy and deficient cytokine production after single treatment.

A longitudinal investigation has been conducted into the cell-mediated immune responses of onchocerciasis patients after a single-dose treatment with ivermectin. Untreated patients tested for delayed cutaneous hypersensitivity (DCH) to seven recall antigens showed lower responses than infection-free control individuals (P less than 0.01), but 6 and 14 months after treatment DCH reactions increased to similar levels to those seen in the controls. The in vitro cellular reactivity to Onchocerca volvulus-derived antigen (OvAg) was reduced in untreated patients as compared with controls, and the lymphocyte blastogenic responses to OvAg and streptolysin-O clearly improved up to 14 months after treatment. Peripheral blood mononuclear cells (PBMC) from untreated patients produced IL-1 beta, tumour necrosis factor-alpha (TNF-alpha) and IL-6 in response to mitogenic stimulation with phytohaemagglutinin (PHA), only low levels of IL-1 beta, IL-2 and TNF-alpha in response to OvAg, but higher amounts of IL-4 and interferon-gamma (IFN-gamma) in response to OvAg than control individuals. After ivermectin treatment, the OvAg-induced production of IL-1 beta and TNF-alpha increased significantly 1 and 14 months after treatment. The PHA-induced production of IL-2 and IL-4 increased 1 month after treatment and remained significantly elevated until 14 months after treatment, whereas the OvAg-specific secretion of IL-2, IL-4 and IFN-gamma did not change after ivermectin treatment. Flow cytometric analysis of lymphocyte-subsets in the peripheral blood of untreated patients revealed a relative and absolute (P less than 0.01) diminution of CD4+ cells and a significantly smaller CD4+/CD8+ cell ratio as compared with controls. By 4 weeks after treatment and thereafter, CD4+ T cells increased relatively and absolutely (P less than 0.01); likewise there was an absolute increase in T-helper-inducer cells (CD4+CD45RO+) and a temporarily improved CD4+/CD8+ cell ratio (P = 0.001). The expression of the low-affinity receptor for IgE (CD23) on total lymphocytes decreased from 14% to 7% by 14 months after treatment. The CD8+ cells and CD3+TCR gamma delta + cells were higher in patients than in controls and both remained elevated until 14 months after treatment. These results suggest a distinctly improved cellular immunity in human onchocerciasis that was facilitated by ivermectin therapy.

Animals↗
PubMed1989

Chemoprophylaxis and immunity to parasitic bronchitis in cattle--a field experiment comparing topical ivermectin and an oxfendazole intraruminal device.

Seeder calves infected with Dictyocaulus viviparus were used to contaminate a field divided into three similar paddocks. Twenty-four autumn-born calves were allocated to three matched groups; one group was given topical ivermectin treatments (0.5 mg/kg) at 3, 8 and 13 weeks after turnout (Day 0); each member of a second group was given an oxfendazole pulse-release intraruminal device (OPRB) at turnout; while a third group was kept as untreated controls to monitor the natural epidemiological pattern of events. Severe pasteurella pneumonia exacerbated by lungworm infection occurred in the controls after Day 24. Two died and repeated doses of antibiotic and anthelmintic therapy were necessary to save the remainder. Clinical signs were much milder in the ivermectin and OPRB groups and resolved with only a single dose of antibiotic. The OPRB group excreted some lungworm larvae at this time, but none was detected in the faeces of the ivermectin group during the grazing season. At housing, five calves from each group and four lungworm-naive calves were challenged with D. viviparus larvae. The infection became patent in all challenge-control calves, but no larvae were passed by any of the trial animals. Post-mortem worm-counts revealed percentage takes for the challenge controls, trial controls, ivermectin and OPRB groups of 16.7, 0.01, 0.9 and 0.2, respectively. All trial groups had therefore developed a substantial immunity.

Administration, Topical↗
PubMed2006

Fexofenadine in horses: pharmacokinetics, pharmacodynamics and effect of ivermectin pretreatment.

The pharmacokinetics and the effects on inhibition of histamine-induced cutaneous wheal formation of the histamine H1-antagonist fexofenadine were studied in horse. The effect of ivermectin pretreatment on the pharmacokinetics of fexofenadine was also examined. After intravenous infusion of fexofenadine at 0.7 mg/kg bw the mean terminal half-life was 2.4 h (range: 2.0-2.7 h), the apparent volume of distribution 0.8 L/kg (0.5-0.9 L/kg), and the total body clearance 0.8 L/h/kg (0.6-1.2 L/h/kg). After oral administration of fexofenadine at 10 mg/kg bw bioavailability was 2.6% (1.9-2.9%). Ivermectin pretreatment (0.2 mg/kg, p.o.) 12 h before oral fexofenadine decreased the bioavailability to 1.5% (1.4-2.1%). In addition, the area under the plasma concentration-time curve decreased 27%. Ivermectin did not affect the pharmacokinetics of i.v. administered fexofenadine. Ivermectin may influence fexofenadine absorption by interfering in intestinal efflux and influx pumps, such as P-glycoprotein and the organic anion transport polypeptide family. Oral and i.v. fexofenadine significantly decreased histamine-induced wheal formation, with a maximal duration of 6 h. A pharmacokinetic/pharmacodynamic link model indicated that fexofenadine in horse has antihistaminic effects at low plasma concentrations (EC50 = 16 ng/mL). However, oral treatments of horses with fexofenadine may not be suitable due to the low bioavailability.

Animals↗
PubMed1997

Ivermectin for the chemotherapy of bancroftian filariasis: a meta-analysis of the effect of single treatment.

The efficacy and safety of ivermectin in the treatment of filariasis due to Wuchereria bancrofti was assessed by a meta-analysis of the results from 15 published clinical trials. Seven hundred and forty-eight microfilaraemic patients were enrolled in 7 dose-finding and 8 comparative studies. Administered as a single dose, ivermectin induced nearly complete clearance of microfilariae from the blood from the first day to 30 days post-treatment, followed by gradual recurrence of microfilaraemia and increase in its intensity. Higher doses of ivermectin showed greater clearance effects and maintained lower microfilaraemia levels for a longer time. The adverse reactions caused by the drug were flu-like, transient, generally mild and well tolerated by patients. The frequency and intensity of adverse reactions were strongly associated with pretreatment microfilaria counts in the blood, but independent of dose. The findings of the meta-analysis suggest that ivermectin given at a single annual dose of 200 micrograms/kg body weight or higher, whether or not in combination with DEC, has great potential for therapeutic strategies to control bancroftian filariasis.

Elephantiasis, Filarial↗
PubMed2004

Impact of ivermectin on illness and disability associated with onchocerciasis.

The Onchocerciasis Control Program (OCP), one of the most successful vertical disease control programs in the history of public health, came to an end in 2003 with devolvement of responsibilities for control program activities passed to the countries affected. Fortunately, 15 years ago the Mectizan Distribution Program (MDP) was founded to provide a complementary approach to controlling the disabling consequences of this parasitic infection. With over 250 million doses of ivermectin distributed over the past 15 years, the MDP is well on its way to both solidifying the progress made by the OCP and extending program reach well beyond the boundaries of the OCP. Through the extensive clinical testing protocols implemented in a variety of countries in Aftica, ivermectin has been proven to be a safe and highly effective treatment for onchocerciasis. Regular distribution to populations living in endemic areas has demonstrated significant reductions in blinding ocular complications, transmission, and disability caused by onchocercal skin disease. As yet undocumented, are the likely significant impact regular population dosing with ivermectin has on intestinal helminth infections, lymphatic filariasis, and human scabies infection. While there are significant barriers to continued program success, focussed attention on expanding and improving community-directed ivermectin distribution is likely to lead to further progress against this resilient infection.

Developing Countries↗
PubMed2004

Additional health and development activities for community-directed distributors of ivermectin: threat or opportunity for onchocerciasis control?

We studied the involvement of community-directed distributors (CDDs) of ivermectin for onchocerciasis control in other health and development activities in Nigeria, Togo and Cameroon. Most CDDs (82%) were involved in additional activities, especially EPI, water and sanitation and community development projects. These activities did not take up much time and were not considered an important burden. Ivermectin treatment coverage did not decline with increasing number of additional activities. Other health programmes are interested in building on the experiences and structures of community-directed treatment with ivermectin and involving CDDs in their health programmes. Some, such as EPI, provide financial incentives. Incentives by other programmes may enhance the performance of CDDs when they are selected on the basis of their CDD status. CDDs, health personnel and community members have very positive attitudes towards greater involvement of CDDs in additional health and development activities. We conclude that additional activities for CDDs do not pose a threat to but rather provide an opportunity to strengthen sustainability and effectiveness of ivermectin treatment.

Adult↗
PubMed2005

Short communication: impact of long-term (14 years) bi-annual ivermectin treatment on Wuchereria bancrofti microfilaraemia.

Ivermectin has been and continues to be extensively used to control onchocerciasis in areas of hyper and mesoendemicity within the African Programme of Onchocerciasis Control. As programmes to eliminate lymphatic filariasis (LF) caused by Wuchereria bancrofti expand, areas of coendemicity with onchocerciasis will be incorporated into LF programmes. This study reports that in villages which were hyperendemic for onchocerciasis after some 14 years of treatment with ivermectin, no W. bancrofti could be detected in a population of 1210 individuals whilst in adjacent villages a prevalence of around 3% was found. Despite the long period of ivermectin treatment Mansonella perstans did not appear to respond to ivermectin in this setting.

Animals↗