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PubMed2001

Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr1 gene.

A subpopulation of collie dogs is extremely sensitive to neurotoxicity induced by ivermectin. The aim of this study was to determine the mechanistic basis for this phenomenon. The multi-drug-resistance gene (mdr1) encodes a large transmembrane protein, P-glycoprotein (P-gp), that is an integral part of the blood-brain barrier. P-gp functions as a drug-transport pump at the blood-brain barrier, transporting a variety of drugs from the brain back into the blood. Since ivermectin is a substrate for P-gp, we hypothesized that ivermectin-sensitive collies had altered mdr1 expression compared with unaffected collies. We report a deletion mutation of the mdr1 gene that is associated with ivermectin sensitivity. The 4-bp deletion results in a frame shift, generating several stop codons that prematurely terminate P-gp synthesis. Dogs that are homozygous for the deletion mutation display the ivermectin-sensitive phenotype, while those that are homozygous normal or heterozygous do not display increased sensitivity to ivermectin.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1985

The efficacy of ivermectin against larvae of the screw-worm fly (Chrysomya bezziana).

An in vitro technique for screening systemic insecticides against larvae of the screw-worm fly, Chrysomya bezziana is described. Susceptibilities of screw-worm larvae of different ages to ivermectin (MK-933) were determined. Based on 24 h larval mortality, the LD50 of 1-,2-,3-,4- and 5-day larvae was 0.01, 0.02, 0.03, 0.2 and 0.4 ppm of ivermectin. LD50 based on adult emergence following treatment of 4- and 5-day larvae was 0.02 and 0.05 ppm. The LD99.9 for 4-day larvae based on 24 h larval mortality and adult emergence was 11.0 and 0.15 ppm respectively and for 5-day larvae, was 44.3 and 0.4 ppm respectively. Pen and field trials with cattle infested with screw-worm fly demonstrated the potential of ivermectin as a systemic insecticide. Dosages of 50, 100 and 200 micrograms/kg, of ivermectin administered subcutaneously to experimentally infested cattle gave complete control for 6, 12 and 14 days respectively. Ivermectin at 200 micrograms/kg caused 100% mortality of screw-worm larvae up to 2 days old at the time of treatment with 70, 64 and 21% mortality of 3-, 4- and 5-day old larvae at the time of treatment. The residual protection from a single dose of 200 micrograms/kg was 16 to 20 days. When bull calves were treated with ivermectin at a dose of 200 micrograms/kg at the time of castration and branding, none of the 77 treated animals sustained a screw-worm strike in the scrotal area compared with 47 strikes (44%) in the 106 control cattle.

Animals↗
PubMed1999

Transmission of Babesia spp by the cattle tick (Boophilus microplus) to cattle treated with injectable or pour-on formulations of ivermectin and moxidectin.

OBJECTIVE: To assess the efficacy of ivermectin and moxidectin to prevent transmission of Babesia bovis and Babesia bigemina by Boophilus microplus to cattle under conditions of relatively intense experimental challenge. DESIGN: Naive Bos taurus calves were treated with either pour-on or injectable formulations of either ivermectin or moxidectin and then exposed to larvae of B microplus infected with B bovis or larvae or adults of B microplus infected with B bigemina. One calf was used for each combination of haemoparasite, B microplus life stage, drug and application route. PROCEDURE: Groups of calves were treated with the test drugs in either pour-on or injectable formulation and then infested with B microplus larvae infected with B bovis or B bigemina. B bigemina infected adult male ticks grown on an untreated calf were later transferred to a fourth group of animals. Infections were monitored via peripheral blood smears to determine haemoparasite transmission. RESULTS: Cattle treated with either pour-on or injectable formulations of ivermectin and moxidectin became infected with B bovis after infestation with infected larvae. Similarly, larvae infected with B bigemina survived to the nymphal stage to transmit the haemoparasite to animals treated with each drug preparation. Cattle treated with pour-on formulations of ivermectin and moxidectin then infested with adult male ticks infected with B bigemina did not become infected with B bigemina whereas those treated with the injectable formulations of ivermectin and moxidectin did show a parasitaemia. CONCLUSIONS: Injectable or pour-on formulations of ivermectin and moxidectin do not prevent transmission of Babesia to cattle by B microplus. Use of these drugs can therefore not be recommended as a primary means of protecting susceptible cattle from the risk of Babesia infection.

Administration, Cutaneous↗
PubMed2001

Reduced efficacy of ivermectin, abamectin and moxidectin against field isolates of Haemonchus contortus.

OBJECTIVES: To investigate the reduced efficacy of ivermectin, abamectin and moxidectin against two field isolates of Haemonchus contortus. These isolates were identified on separate properties in the New England region of New South Wales. PROCEDURE: Reduced efficacy of macrocyclic lactone anthelmintics against two field isolates of H contortus was suspected. These isolates were obtained from sheep on separate farms and pen trials were performed to investigate the efficacy of macrocyclic lactones. The percentage efficacy was calculated for moxidectin, ivermectin and closantel against the isolate from one farm (VHR23) and for moxidectin, ivermectin and abamectin against the isolate from the second (VHR29). The persistent activity of moxidectin against both isolates was investigated. RESULTS: Ivermectin and closantel were found to have efficacies below 80% against established populations of VHR23. Moxidectin was effective against an established population of VHR23 but the persistent activity was reduced to 7 days. Moxidectin was also found to be effective against established populations of VHR29, however, ivermectin and abamectin were found to have efficacies below 80%. There was no evidence of persistent activity of moxidectin against VHR29. CONCLUSION: A reduction in efficacy of abamectin and/or ivermectin against field isolates of H. contortus was identified from two farms in the New England region of New South Wales. The persistent effect of moxidectin was reduced against both isolates.

Animals↗
PubMed2005

Functional properties of internalization-deficient P2X4 receptors reveal a novel mechanism of ligand-gated channel facilitation by ivermectin.

Although P2X receptors within the central nervous system mediate excitatory ATP synaptic transmission, the identity of central ATP-gated channels has not yet been elucidated. P2X(4), the most widely expressed subunit in the brain, was previously shown to undergo clathrin-dependent constitutive internalization by direct interaction between activator protein (AP)2 adaptors and a tyrosine-based sorting signal specifically present in the cytosolic C-terminal tail of mammalian P2X(4) sequences. In this study, we first used internalization-deficient P2X(4) receptor mutants to show that suppression of the endocytosis motif significantly increased the apparent sensitivity to ATP and the ionic permeability of P2X(4) channels. These unique properties, observed at low channel density, suggest that interactions with AP2 complexes may modulate the function of P2X(4) receptors. In addition, ivermectin, an allosteric modulator of several receptor channels, including mammalian P2X(4), did not potentiate the maximal current of internalization-deficient rat or human P2X(4) receptors. We demonstrated that binding of ivermectin onto wild-type P2X(4) channels increased the fraction of plasma membrane P2X(4) receptors, whereas surface expression of internalization-deficient P2X(4) receptors remained unchanged. Disruption of the clathrin-mediated endocytosis with the dominant-negative mutants Eps15 or AP-50 abolished the ivermectin potentiation of wild-type P2X(4) channel currents. Likewise, ivermectin increased the membrane fraction of nicotinic alpha7 acetylcholine (nalpha7ACh) receptors and the potentiation of acetylcholine current by ivermectin was suppressed when the same dominant-negative mutants were expressed. These data showed that potentiation by ivermectin of both P2X(4) and nalpha7ACh receptors was primarily caused by an increase in the number of cell surface receptors resulting from a mechanism dependent on clathrin/AP2-mediated endocytosis.

Adenosine Triphosphate↗
PubMed2001

Successful treatment of scabies with oral ivermectin in Nigeria.

Currently, several topical scabicides are available but there is yet no oral or parenteral drug which has been established for the treatment of scabies in Nigeria. Ivermectin which is a modified avermectin, known to be an ectoparasiticidal agent in animals, has been used in adults for systemic parasitosis. In Nigeria, 25% benzyl benzoate is being extensively used for the treatment of scabies in adults. It is effective and readily available. The present study was carried out to evaluate the efficacy and safety of ivermectin in the treatment of patients with scabies at the skin clinic of the University of Nigeria Teaching Hospital, Enugu. Fifty-eight patients with scabies were recruited for the study; 13 (22.4%) were children aged between 5-14 years. Oral ivermectin was given in a single dose of 200 [microg/kg body weight to 29 patients. The remaining 29 patients had to apply 25% benzyl benzoate emulsion. All patients received a full physical and dermatological examination prior to onset of treatment and weekly for 4 weeks. Skin scrapings were taken to confirm the diagnosis of scabies. There was a 93% resolution of pruritus with ivermectin and 48% with benzyl benzoate. No side effects were observed with ivermectin. Our results show that oral ivermectin is a promising, effective and safe alternative in both children and adults of Nigeria when compared to 25% benzyl benzoate topical application.

Administration, Oral↗
PubMed2003

Impact of long-term ivermectin (Mectizan) on Wuchereria bancrofti and Mansonella perstans infections in Burkina Faso: strategic and policy implications.

Parasitological and clinical surveys were used to determine the long-term impact of ivermectin on the prevalence of Wuchereria bancrofti and Mansonella perstans filarial infections, when the drug was given under community-directed-treatment strategies for onchocerciasis control. The study was undertaken in 11 communities in south-western Burkina Faso. Six of the villages investigated had been treated with ivermectin at least once a year for five of 6 years, with a mean coverage of approximately 65% in each round. The other five, adjacent villages, which were matched with the ivermectin-treated communities by size, ethnicity and social and economic activities, had never been treated because they were not endemic for onchocerciasis. Each subject was checked by the microscopical examination of a smear of 'night' blood, by measurement of the level of circulating antigens from adult W. bancrofti, and by clinical examination for hydrocele (if male) and lymphoedema. The prevalences of lymphoedema and hydrocele in the treated villages were similar to those in the untreated. The prevalences and intensities of W. bancrofti and M. perstans microfilaraemia were, however, significantly lower in the ivermectin-treated communities. The implications of this study are discussed in relation to the old Onchocerciasis Control Programme (OCP) and to the ongoing African Programme for Onchocerciasis (APOC), where extensive and sustained ivermectin distribution is planned through community-based treatment programmes. As with onchocerciasis in Africa, the success of annual treatments to control lymphatic filariasis will depend not only on the number of regular rounds of treatment given but on adequate coverages being achieved in each round. Wherever ivermectin is being distributed alone, for onchocerciasis control, its impact on other filarial infections, notably W. bancrofti, should be evaluated routinely. Any opportunity to add donated albendazole to such distributions should be taken, both to limit the transmission of W. bancrofti and for the wider public-health benefits.

Adolescent↗
PubMed2004

Mass treatment of onchocerciasis with ivermectin: should people with epilepsy and/or growth-retardation syndromes be excluded?

In many areas of Africa where human onchocerciasis is endemic there are now programmes for mass treatment with ivermectin (Mectizan), to eliminate the disease as a public-health problem. To determine whether those with epilepsy and/or growth-retardation syndromes (GRS) should be excluded from such mass drug administrations, literature searches of the standard biomedical databases were performed for all relevant articles published in English or French before January 2003. Cross-referencing and the retrieving of articles recommended by experts completed the search. The literature review revealed that there is insufficient evidence for an association between onchocerciasis and epilepsy or GRS. Since ivermectin does not normally cross the blood-brain barrier, the drug is unlikely to have direct pro- or anti-convulsive activity. Furthermore, an estimated 1-2 million epileptics in Africa have been treated with ivermectin, in onchocerciasis-control programmes, without any reports of serious adverse events (SAE) to the passive surveillance system for such events. As there are few data on the prevalence of GRS in Africa, it is difficult to estimate the number of GRS cases who have been treated with ivermectin or the incidence of ivermectin-related SAE among such cases. Epileptics should not be excluded from mass treatments with ivermectin unless they are actively seizing or postictal. Although those with GRS associated with chronic wasting, with or without epilepsy, should be excluded, they should be eligible for clinic-based treatment if the diagnosis of onchocerciasis is confirmed and the benefits of treatment are deemed to outweigh any potential risks.

Africa↗
PubMed2005

Significant decrease in the prevalence of Wuchereria bancrofti infection in anopheline mosquitoes following the addition of albendazole to annual, ivermectin-based, mass treatments in Nigeria.

A prospective entomological survey was conducted in four sentinel villages in central Nigeria from 1999-2002, to assess the impact of annual, single-dose, mass drug administrations (MDA), with a combination of ivermectin and albendazole, on the transmission of Wuchereria bancrofti. As they were also endemic for human onchocerciasis, the four villages had received annual MDA based on ivermectin alone for 7 years prior to the addition of albendazole. Resting Anophelines gambiae s. l., An. funestus and Culex species were collected from 92 sequentially sampled households and dissected. Mosquitoes harbouring any larval stage of W. bancrofti were classified as 'infected', and those containing the third-stage larvae of the parasite were classified as 'infective'. Over the 41-month observation period, 4407 mosquitoes were captured and dissected, of which 64% were An. gambiae s. l., 34% An. funestus, and 1% Culex species. The baseline data, from dissections performed before the addition of albendazole to the MDA, showed high prevalences of mosquito infection (8.9%) and infectivity (2.9%), despite apparently good treatment coverages during the years of annual ivermectin monotherapy. Only the anopheline mosquitoes were found to harbour W. bancrofti larvae. After the third round of MDA with the ivermectin-albendazole combination, statistically significant decreases in the prevalences of mosquito infection (down to 0.6%) and infectivity (down to 0.4%) were observed (P<0.0001 for each). The combination of albendazole and ivermectin appears to be superior to ivermectin alone for reducing the frequency of W. bancrofti infection in mosquitoes.

Albendazole↗
PubMed2004

Efficacy and safety of ivermectin and thiabendazole in the treatment of strongyloidiasis.

Treatment of strongyloidiasis has been traditionally based on thiabendazole, despite its frequent gastrointestinal side effects and failure to achieve eradication of the parasite from faeces in approximately 30% of cases. Ivermectin has been shown to be more effective for treating chronic uncomplicated strongyloidiasis. The efficacy and tolerability of these drugs in a series of patients treated from 1999 to 2002 at the Oliva Health Centre, Valencia, Spain, are reported. A total of 88 patients diagnosed of strongyloidiasis were treated using the following regimens: thiabendazole 25 mg/kg/12 h for 3 consecutive days in 31 patients; ivermectin 200 mug/kg as a single dose in 22 patients; and ivermectin 200 mug/kg for 2 consecutive days in 35 patients. The efficacy and side effects were recorded. A total of 65 patients were male, and 23 female. The mean age was 64 +/- 12 years. Of the patients, 44 had worked barefoot in rice fields. Among the 31 patients treated with thiabendazole, 25 (78%) met the criteria for cure (the absence of parasite in faeces after examination of three samples collected on alternate days), and 5 (16%) experienced side effects (asthenia, epigastralgia and disorientation). Of the 22 patients treated with ivermectin on a single day, 17 (77%) met the criteria for cure, and 2 (9%) reported side effects (dizziness, dyspepsia). Among the 35 patients treated with ivermectin on 2 consecutive days, 100% met the criteria for cure, and 0% experienced side effects. In chronic uncomplicated strongyloidiasis, a treatment regimen consisting of ivermectin 200 mug/kg for 2 consecutive days provided the best results with regard to efficacy and tolerability. When the eosinophilia continued after treatment, we observed a high percentage of not-cure rate (7 of 9 patients, 77%).

Animals↗
PubMed2001

Dynamics of the antibody response in cattle infested by Hypoderma (Diptera: Oestridae) after a treatment with injectable and pour-on ivermectin.

The dynamics of the anti-Hypoderma antibody response after a treatment with injectable and pour-on ivermectin against first instars of Hypoderma sp. were determined in naturally infested cows. Cattle were randomly assigned to three groups: group 1, which served as an untreated control; group 2, treated with pour-on ivermectin at a dose of 500 microg/kg of body weight, and group 3, which received 200 microg/kg of body weight of ivermectin by subcutaneous injection. Both ivermectins showed total efficacy against L-1 of Hypoderma sp. In untreated control animals, grubs became detectable in the 2 mo after treatment. Indirect enzyme-linked immunosorbent assay (ELISA) showed a significant increase in group 3 antibody levels 1 mo after treatment, whereas in group 2 the increase was not significant. Following the peak of anitibody activity in group 3, antibody levels declined at a faster rate than in those treated topically. In both treated groups, cattle remained serologically positive for 4 mo after ivermectin treatment. Thus, serological surveillance programs for cattle grubs conducted during this posttreatment period will not be influenced by treatment with ivermectin. The persistence of antibody levels after larval destruction makes the indirect ELISA unsuitable for the prediction of the efficacy of treatment.

Animals↗
PubMedDate not supplied

Ivermectin toxicity in 17 collies.

Ivermectin is widely used in veterinary medicine as an anthelminthic and generally has a wide margin of safety, but Collies are prone to ivermectin toxicity. Two groups of Collies were presented to the University of California Veterinary Medical Teaching Hospital (VMTH) with ivermectin toxicity. The medical records of the 2 groups of Collies were reviewed retrospectively. Group I comprised 5 adult Collies that received at least 400 microg/kg ivermectin p.o. and were presented to the VMTH 3 hours after intoxication. These Collies showed marked clinical signs on presentation. Three of these dogs required mechanical ventilation and were euthanized for financial reasons; the remaining 2 dogs were comatose but recovered in 5-7 days. Group II was comprised of 12 adult Collies presented to the VMTH 2 days (n = 10) and 5 days (n = 2) after subcutaneous injection of 200-250 microg/kg ivermectin. These animals showed greater variation in severity of illness among individuals; 5 animals progressed to stupor or coma, whereas 4 animals remained ambulatory. Most of these dogs' clinical signs deteriorated from the day of intoxication until approximately day 6, from which time they showed gradual but steady improvement. All of the Collies in this group survived, but it took 3 weeks for most of them to recover. Collies suffering from ivermectin toxicity can have a severe and prolonged clinical course requiring intensive nursing care. Respiratory, cardiovascular, and nutritional support may all be required. With appropriate care, however, the prognosis for complete recovery is good.

Administration, Oral↗
PubMed2006

Evaluation of a covered-rod silicone implant containing ivermectin for long-term prevention of heartworm infection in dogs.

OBJECTIVE: To evaluate use of covered-rod (CR) silicone implants containing ivermectin for long-term prevention of infection with Dirofilaria immitisin dogs. ANIMALS: 145 adult male and female dogs. PROCEDURES: Dogs received implants of different sizes, and ivermectin concentrations and serum ivermectin concentrations were monitored for 16, 57, and 56 weeks, respectively, in 3 preclinical dose selection studies. Ability of implants to prevent infection with D immitis was evaluated in 2 further studies; dogs were challenged with 50 infective third-stage larvae 52 weeks after implant administration and necropsied 145 days after challenge, and the total number of adult heartworms was counted. A field study was then undertaken in which client-owned dogs received an implant and plasma samples were collected at intervals until week 52 for ivermectin analysis and heartworm antigen determination. RESULTS: Use of the implants resulted in maintenance of an ivermectin concentration > or = 0.2 ng/mL for 12 months. In challenge studies, no treated dogs had adult heartworms, in contrast to untreated dogs, which all had adult heartworms at necropsy. In the field study, dogs treated with an implant had negative results of heartworm antigen testing for 12 months. CONCLUSIONS AND CLINICAL RELEVANCE: The CR silicone implant containing 7.3 mg of ivermectin was 100% effective in preventing experimental infection with D immitislarvae and resulted in negative results for heartworm antigen in a field trial. This product has the potential to alleviate poor owner compliance with monthly prevention regimens.

Animals↗
PubMed2000

Relative cost-effectiveness of treatment of feedlot calves with ivermectin versus treatment with a combination of fenbendazole, permethrin, and fenthion.

OBJECTIVE: To compare growth performance, animal health characteristics, and carcass characteristics of feedlot calves treated with ivermectin topically with that of feedlot calves treated with a combination of fenbendazole orally and permethrin and fenthion topically. DESIGN: Clinical trial. ANIMALS: 14,184 British crossbred steer calves (mean weight, 286 kg [630 lb]) in 30 pens at a commercial feedlot in Nebraska. PROCEDURE: On arrival at the feedlot, calves were randomly assigned to be treated with ivermectin topically or with a combination of fenbendazole orally and permethrin and fenthion topically (control). At the time of assignment to treatment groups, fecal samples were collected from 5% of the calves. Growth performance, carcass characteristics, and health information were recorded. RESULTS: Geometric mean fecal egg counts at the time of arrival at the feedlot were not significantly different between groups. Final weight, weight gain, average daily gain, and the dry matter intake-to-gain ratio were significantly improved for calves in the ivermectin group. The percentage of carcasses classified as quality grade choice was higher for the ivermectin group than the control group; however, the percentage of carcasses classified as yield grade 1 and the dressing percentage were higher for the control group than for the ivermectin group. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that topical administration of ivermectin to feedlot calves is relatively more cost-effective than administration of a combination of fenbendazole orally and permethrin and fenthion topically.

Administration, Oral↗
PubMed1999

Effects of continuous ivermectin treatment from birth to puberty on growth and reproduction in dairy heifers.

The effect of continuous ivermectin treatment from birth to puberty on growth and reproductive performance was studied in Holstein heifer calves grown on pastures in comparison to naturally nematode-infected, untreated animals. Ivermectin effectively abated the presence of nematode eggs in feces. Eggs per gram (EPG) in parasitized animals increased rapidly from wk 12 to 18 of age and then decreased. Animals treated with ivermectin grew faster than untreated ones, and differences in body weight became significant at 6 wk of life, even before eggs appeared in the feces of either treatment group. Ivermectin-treated heifers reached puberty 3 wk earlier than infected ones as assessed with serum progesterone concentrations (ivermectin, 30.4 +/- .8 vs untreated, 33.7 +/- 1.3 wk of age). This delay was not directly related to body weight. In addition, pelvic area at 39 wk and at 15 mo of age was increased in treated heifers (8 and 11%, respectively) compared with parasitized animals. No differences in the wither heights were observed. We conclude that ivermectin treatment in dairy heifers may increase growth rate during development, advance the onset of ovarian function, and positively affect yearling pelvic area.

Animals↗
PubMed1988

Ivermectin in loiasis and concomitant O. volvulus and M. perstans infections.

Two clinical studies were carried out in Gabon, Africa to evaluate the efficacy, safety, and tolerability of ivermectin in the treatment of patients with Loa loa infection. In the first study, 35 patients received single oral doses of ivermectin, 5-200 mcg/kg body weight. Blood microfilariae levels did not decrease after a single oral 5, 10, 30, or 50 mcg/kg dose of ivermectin, but levels did decrease after doses of 100, 150, and 200 mcg/kg. The most efficacious dose was 200 mcg/kg; mean blood microfilariae levels decreased to 12% of mean pretreatment values by day 15 and remained decreased for 28 days. A second study evaluated the safety and efficacy of ivermectin in patients with multifilarial infections. All 17 patients had concomitant Loa loa and O. volvulus infection. M. perstans affected 5 of the patients. Sixteen patients also had infections due to intestinal nematodes. The patients each received single oral doses of 200 mcg/kg ivermectin. Ten days later, the mean Loa loa blood microfilariae level had decreased to 20% of the mean pretreatment level. O. volvulus dermal microfilariae densities were reduced to 2% of the pretreatment levels. A minimal increase in blood microfilaria levels was observed on day 28. In contrast, dermal microfilariae levels remained near zero for the duration of the study. Intestinal infection due to Ascaris was eradicated in all of the affected patients by day 23; efficacy against Trichuris and hookworm infections, however, was poor. All patients tolerated ivermectin well including those with multiple infections.

Adult↗
PubMed1992

Brugia malayi: ivermectin inhibits the exsheathment of microfilariae.

Brugia malayi-infected microfilaremic jirds (Meriones unguiculatus) were treated with ivermectin at a single dose of 200 micrograms/kg of body weight injected subcutaneously. Susceptible Aedes aegypti mosquitoes were fed on treated jirds 24 hours later. Mosquitoes fed on untreated jirds served as controls. Infected mosquitoes were dissected at 1, 3, 24, 48, 72, and 96 hr after the blood meal, and differential counts of sheathed microfilariae, exsheathed microfilariae, and cast sheaths were performed using fluoresceinated wheat germ agglutinin. Microfilariae failed to exsheath in mosquitoes fed on ivermectin-treated jirds. Microfilariae from ivermectin-treated jirds also did not exsheath in vitro in the presence of 10 mM CaCl2, whereas 85-90% of sheathed microfilariae from untreated jirds exsheathed in vitro. In addition, sheathed microfilariae from untreated jirds, when pretreated in vitro with ivermectin at 0.25, 0.5, or 1 microgram/ml, lost their ability to exsheath in vitro in the presence of 10 mM CaCl2. However, ivermectin treatment had no effect on exsheathing of microfilariae when incubated with papaya protease. Thus, ivermectin appears to inhibit the intrinsic exsheathing process of microfilariae in the mosquito host, thereby blocking their development and further transmission of infection.

Aedes↗
PubMed1994

Ivermectin treatment of bancroftian filariasis in Recife, Brazil.

To determine the effectiveness of single oral dosages of ivermectin ranging between 20 and 200 micrograms/kg and to make detailed observations of both the kinetics of parasite killing and the adverse reactions induced by treatment, the present double-blind study on ivermectin treatment of lymphatic filariasis caused by Wuchereria bancrofti was undertaken with 43 microfilaremic patients in Recife, Brazil. Follow-up at one year indicated equivalent efficacy for the 20-, 100-, and 200-micrograms/kg drug dosages in reducing microfilaremia to geometric means of 13-25% of pretreatment levels. Adverse clinical reactions (predominantly fever, headache, weakness, and myalgia) occurred to some degree in almost all patients but generally lasted only 24-48 hr and were easily managed symptomatically. Adverse reactions were significantly milder in those receiving the lowest (20 micrograms/kg) ivermectin dose, and they were significantly correlated with individuals' pretreatment microfilaremia levels in all groups. Posttreatment eosinophilia was a regular feature of the response to treatment, with the magnitude and kinetics also proportional to pretreatment microfilarial levels. Transient pulmonary function abnormalities (16 of 42, 38%), liver enzyme elevations (10 of 43, 23%), and hematuria (9 of 42, 22%) developed posttreatment, but all cleared without significant complications. The results indicate that W. bancrofti from Brazil is similar to strains of the parasites studied elsewhere in susceptibility to ivermectin, that the drug's systemic adverse reactions are essentially those resulting from parasite clearance, and that the intensity of these reactions can be significantly reduced by using the low (20 micrograms/kg) dose of ivermectin. This detailed dose-finding study provides information necessary for developing optimal regimens to treat bancroftian filariasis with ivermectin either alone or in combination with other medications.

Adult↗