Tolerability of ivermectin in gnathostomiasis

At present, no universally-accepted effective treatment for cutaneous gnathostomiasis is available. At the Hospital for Tropical Diseases, Mahidol University, albendazole 400 mg twice a day for 14 days is commonly prescribed for patients diagnosed with cutaneous gnathostomiasis. The efficacy of albendazole to induce outward migration of the parasite was less than or around 20% in 2 studies. Research for alternative, more efficacious treatment, is needed. In this prospective open-labeled study, we assessed the safety of ivermectin in 20 Thai patients diagnosed with cutaneous gnathostomiasis. Ivermectin, one time only, at dosages of 50, 100, 150, or 200 microg/kg bodyweight, was given orally to 4 groups of patients, 5 patients each group. Adverse events were recorded and laboratory tests were obtained before and after treatment. No serious adverse events occurred in this study. Forty adverse events were possibly related to ivermectin. The adverse events were malaise (35%), myalgia (30%), drowsiness (30%), pruritus (20%), nausea/vomiting (20%), dizziness (15%), diarrhea (15%), feeling of shortness of breath (10%), feeling of palpitations (10%), constipation (5%), anorexia (5%), and headache (5%). These adverse events were self-limited and not dose-related. Laboratory abnormalities were found in 3 patients (15%). Transient microscopic hematuria, pyuria, and mildly elevated liver enzymes were found in 1 patient each. Ivermectin single dose, of 50,100, 150, and 200 microg/kg bodyweight, is considered safe in Thai patients. Future trials of ivermectin on human gnathostomiasis may be performed using dosages up to 200 microg/kg bodyweight.     

Efficacy of ivermectin treatment of cutaneous gnathostomiasis evaluated by placebo-controlled trial

Previous studies have revealed that ivermectin treatment for gnathostomiasis can reduce parasitic loads in animals and make recurrent subcutaneous swelling subside in 76% of patients. Our study aimed to evaluate the efficacy of ivermectin for cutaneous gnathostomiasis treatment in a placebo-controlled trial. This study was a prospective randomized placebo-controlled study performed at The Bangkok Hospital for Tropical Diseases, Mahidol University, Thailand. Thirty patients with a serologically confirmed diagnosis of cutaneous gnathostomiasis were enrolled. Seventeen patients in the ivermectin treated group received a single dose of 12 mg ivermectin (200 microg/kg bodyweight), while 13 patients in the control group received a single dose of 40 mg of vitamin B1. The follow-up period was 1 year. Of the 17 patients, 7 (41.2%) responded to ivermectin, while no patient responded to placebo. The mean (95% Cl) time to the first recurrence of subcutaneous swelling with ivermectin and in the placebo groups were 257 (184-331) and 146 (42-250) days, respectively, (p=0.102). Although this study revealed no significant difference in the mean time to first recurrence of swelling between the ivermectin and placebo groups, there was a trend towards ivermectin efficacy against gnathostomiasis in previous animal and human studies. Further studies with different doses of ivermectin and larger sample sizes, and close monitoring for ivermectin tolerability and treatment response are necessary to confirm an efficacy of ivermectin.     

Double-dose ivermectin vs albendazole for the treatment of gnathostomiasis

A comparative study was performed for the treatment of gnathostomiasis patients with ivermectin 0.2 mg/kg for 2 days in 15 patients vs albendazole 400 mg twice daily for 21 days in 14 patients. The ivermectin and albendazole gave cure rates of 100% and 78.5%, respectively, however the difference was not statistically significant between the two drugs (Fisher's exact, p=0.0996). One year after treatment, the patients who had no migratory swellings and a drop in ELISA titers or a negative immunoblot test were considered to be cured. The side effect of ivermectin for two days was dizziness. The side effects of albendazole were nausea, dizziness, and an increased alkaline phosphatase.     

Comparison of ivermectin and albendazole treatment for gnathostomiasis

Comparative treatment of ivermectin in 21 patients (Group 1) and albendazole in 49 patients (Group 2) of gnathostomiasis gave the cure at 95.2% and 93.8% respectively. The ELISA OD and eosinophil counts were reduction after treatment. Side effects in ivermectin were hypotention, dizziness, weakness and diuresis; and side effects of albendazole were nausia, dizziness and increased alkaline phosphatase in two cases. Ivermectin should be an effective drug againts gnathostomiasis and more convenient in treatment single dose.     

Two-year follow-up of the microfilaraemia of asymptomatic brugian filariasis, after treatment with two, annual, single doses of ivermectin, diethylcarbamazine and albendazole, in various combinations

Repeated, single, oral doses of combinations of ivermectin, diethylcarbamazine (DEC) or albendazole are recognized as important tools for parasite control in lymphatic filariasis. In order to assess the effects of re-treatment using these combinations in Brugia malayi infections, 40 asymptomatic microfilaraemics were re-treated at the end of the first year, with an additional, single, dose of the combination they had previously received. They were then followed-up for another year. The subjects, of both sexes and aged 14-70 years, each received a two-drug combination: ivermectin (200 micrograms/kg) with DEC (6 mg/kg); ivermectin (200 micrograms/kg) with albendazole (400 mg); or DEC (6 mg/kg) with albendazole (400 mg). The kinetics of microfilarial clearance were similar to that seen during the first treatment, the members of the two groups given DEC having less intense microfilaraemias, 1 year after the re-treatment, than those given ivermectin with albendazole (P < 0.001 for each comparison). At this time, the two DEC groups also had a higher proportion of amicrofilaraemic individuals (22 of 26) than the ivermectin + albendazole group (three of nine). There were fewer adverse reactions in all the groups after re-treatment than seen after the first treatment. In countries such as India, where there is no co-endemicity of onchocerciasis or loiasis, the options for control programmes in areas where brugian filariasis is endemic are DEC alone or DEC in combination with ivermectin or albendazole. Where there is no access to ivermectin, transmission control must be based on DEC alone or in combination with albendazole.     

Disseminated strongyloidiasis successfully treated with extended duration ivermectin combined with albendazole: a case report of intractable strongyloidiasis

We describe a patient with an overlapping syndrome disseminated strongyloidiasis and gram-negative sepsis. She was previously treated with albendazole 400 mg/day 14 days before admission without success. This admission, she was treated with a combination of oral ivermectin (injectable solution form), with a dosage of 200-400 microg/kg/day, and albendazole for 14 days. Strongyloides larvae disappeared from the stool by day 4 and from the sputum by day 10. No side effects were encountered during hospitalization or at the 1-month follow-up visit.     

Parenteral administration of ivermectin in a patient with disseminated strongyloidiasis

We report the case of a 23-year-old Caribbean man with disseminated strongyloidiasis (co-infected with human T cell lymphotropic virus I/II)), severe hypoalbuminemia, and a paralytic ileus. Subcutaneous ivermectin (200 microg/kg) was administered daily for 14 days because of the inability to effectively administer oral albendazole and oral ivermectin. Three hours after the third daily dose of oral ivermectin, the serum ivermectin concentration was only 0.8 ng/mL, but it increased several fold to 5.8 ng/mL 16 hours after the first dose of subcutaneous ivermectin. During the course of subcutaneous treatment, ivermectin clearance was higher than expected (46.0 L/hour, normal = 31.8 L/hour). This is likely the result of severe hypoalbuminemia since ivermectin is highly protein bound. The ability to achieve adequate levels of ivermectin after oral administration in patients with disseminated strongyloidiasis may be impaired, highlighting the need for alternative routes of administration of ivermectin in these patients.     

Treatment of human scabies with oral ivermectin

Thirty-eight patients with scabies (21 males and 17 females) received oral ivermectin in two doses of 200 microg/kg at 7 days interval. Excellent results were achieved in 29 cases (76.34%), improvement in 6 (15.78%) and poor responses in 3 (7.88%). Tolerance was satisfactory-excellent in 32 patients (84.2%). The effectiveness and safety of the drug described in previous studies are confirmed by the present results.     

Treatment of cutaneous larva migrans.

Cutaneous larva migrans caused by the larvae of animal hookworms is the most frequent skin disease among travelers returning from tropical countries. Complications (impetigo and allergic reactions), together with the intense pruritus and the significant duration of the disease, make treatment mandatory. Freezing the leading edge of the skin track rarely works. Topical treatment of the affected area with 10%-15% thiabendazole solution or ointment has limited value for multiple lesions and hookworm folliculitis, and requires applications 3 times a day for at least 15 days. Oral thiabendazole is poorly effective when given as a single dose (cure rate, 68%-84%) and is less well tolerated than either albendazole or ivermectin. Treatment with a single 400-mg oral dose of albendazole gives cure rates of 46%-100%; a single 12-mg oral dose of ivermectin gives cure rates of 81%-100%.     

伊维菌素和阿苯达唑伍用治疗钩虫、鞭虫感染的疗效观察

目的　观察伊维菌素和阿苯达唑伍用驱治钩虫和鞭虫感染的疗效。　方法　用伊维菌素 6mg和 12mg分别伍用阿苯达唑 2 0 0mg顿服治疗钩虫感染者 ,伊维菌素 12mg伍用阿苯达唑 2 0 0mg顿服治疗鞭虫感染者 ;同时 ,用阿苯达唑40 0mg顿服分别治疗钩虫和鞭虫感染者。用虫卵阴转率评价疗效。　结果　 6mg和 12mg伊维菌素伍用阿苯达唑治疗钩虫感染者 ,其虫卵阴转率分别为 93 .3 %和 95 .5 % ,12mg伊维菌素伍用阿苯达唑治疗鞭虫感染者 ,其虫卵阴转率为 94.3 % ;而单用阿苯达唑治疗钩虫和鞭虫感染者 ,其虫卵阴转率分别为 66.7%和 47.1%。　结论　伊维菌素和阿苯达唑伍用驱治钩虫和鞭虫感染的效果良好 ,两药有协同作用 ,而不良反应轻微、短暂。     

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.     

Efficacy of albendazole and its combinations with ivermectin or diethylcarbamazine (DEC) in the treatment of Trichuris trichiura infections in Sri Lanka

The efficacy of the drugs currently available for treatment of infection with Trichuris trichiura is low compared with that of the drugs used against roundworm and hookworm. Single-dose combinations of albendazole with ivermectin or of albendazole with diethylcarbamazine (DEC) have recently been seen to produce raid and sustained reductions in Wuchereria bancrofti microfilaraemia. This observation prompted the present study, on the efficacy of these combinations against trichuriasis. The drug regimens tested were albendazole (400 mg) alone, albendazole (400 mg) with ivermectin (200 micrograms/kg), and albendazole (400 mg) with DEC (6 mg/kg). Most (155) of the 176 children (4-14 years of age) who each provided a single, pre-treatment, stool sample were found positive for Trichuris ova. These 155 were each randomly allocated to one of the three treatment groups and checked for infection 3 weeks post-treatment, again by a single stool examination. Single-dose therapy with albendazole plus ivermectin produced a 'cure rate' (79.3%) and an egg-reduction rate (93.8%) which were significantly higher than the corresponding rates produced by albendazole alone or albendazole plus DEC (P < 0.01 for each). The efficacies of albendazole with DEC and of albendazole alone were statistically equivalent. Single-dose treatment with the albendazole-ivermectin combination appears to be highly effective against trichuriasis and could prove valuable for routine use.     

Treatment of the microfilaraemia of asymptomatic brugian filariasis with single doses of ivermectin, diethylcarbamazine or albendazole, in various combinations

Several new chemotherapeutic tools are now available for the control of lymphatic filariasis. Combinations of single doses of antifilarial drugs are generally superior to single drugs. The efficacy and safety of albendazole in combination with diethylcarbamazine (DEC) or ivermectin, for the treatment of Brugia malayi infection, were investigated, for the first time, in an open, hospital-based study. Fifty-one asymptomatic microfilaraemics (with 108-4034 microfilariae/ml; median = 531) of both sexes and aged 14-70 years were randomly allocated to receive single-dose treatments of ivermectin (200 micrograms/kg) with diethylcarbamazine (DEC; 6 mg/kg), ivermectin (200 micrograms/kg) with albendazole (400 mg), DEC (6 mg/kg) with albendazole (400 mg), or albendazole (400 mg) alone. Albendazole alone had no effect on the microfilarial levels at the 1-year follow-up but both groups given DEC had significantly lower microfilaraemias (P < 0.015 and P < 0.02) than that given ivermectin with albendazole. Overall, 47%-64% of those given DEC but only 14% of those given ivermectin with albendazole appeared to be amicrofilaraemic 1 year post-treatment. The adverse reactions seen in the study were mild, transient and qualitatively similar to those seen earlier with ivermectin and DEC. The combination of DEC and albendazole, both well tested drugs, offers a new option for countries such as India where there is no onchocerciasis or loiasis and where ivermectin may not be immediately available. The direct and indirect effects of albendazole on intestinal helminths would be additional benefits.     

The co-administration of ivermectin and albendazole--safety,pharmacokinetics and efficacy against Onchocerca volvulus

A randomized, double-blind, placebo-controlled trial was conducted, to determine whether the co-administration of ivermectin with albendazole is safe and more effective against Onchocerca volvulus than ivermectin alone, and whether a significant pharmacokinetic interaction occurs. Forty-two male onchocerciasis patients received ivermectin (200 mug/kg) alone, albendazole (400 mg) alone or the combination. Safety was determined from the results of detailed clinical and laboratory examinations before treatment, during hospitalization and on day 30. Microfilaricidal efficacy was estimated from the reductions in skin counts between day 0 (pretreatment) and day 30. To determine efficacy against the adult worms, two independent observers examined histology slides prepared from nodules excised on day 180; changes in the skin counts of skin microfilariae between days 30 and 365 provided additional indicators of the level of adulticidal activity. Pharmacokinetic parameters for ivermectin and albendazole sulphoxide were defined over 72 h post-treatment. The co-administration of ivermectin with albendazole did not produce more severe adverse effects than ivermectin alone. Both nodule examiners found that the combination was not macrofilaricidal and that it was not clearly superior to ivermectin alone in the effects on reproductive activity; this was supported by the similar efficacy of the two regimens in the suppression of skin microfilariae. There was no significant pharmacokinetic interaction. Although the co-administration of ivermectin with albendazole appears safe, it offers no advantage over ivermectin alone in the control of onchocerciasis. The combination does not require an alteration in the dosage of either component.     

Comparative studies on the efficacy of three anthelminthics on treatment of human strongyloidiasis in Okinawa, Japan

A study was undertaken to compare the efficacy of three drugs in the treatment of uncomplicated strongyloidiasis in Okinawa, Japan. Two hundred and eleven patients with confirmed Strongyloides stercoralis infection were given either ivermectin, 6 mg in a single dose, albendazole, 400 mg/day for 3 days or pyrvinium pamoate, 5 mg/kg/day for 3 days. For each treatment, the same regimen was repeated once 2 weeks later. Efficacy was evaluated at 2 weeks, 6 months and 12 months after the second course of treatment. Each follow-up examination included a parasitological examination of z stool specimens, using the agar-plate culture method. Coprological cure was obtained in 65 of the 67 patients treated with ivermectin (97.0%), in 65 of the 84 patients treated with albendazole (77.4%) and only in 14 of the 60 patients who were given pyrvinium pamoate (23.3%). The cure rates were lower in males and in the patients with concurrent HTLV-1 infection. An epidemiological feature of Strongyloides infection in recent Okinawa might allow workers to evaluate the exact efficacy of the treatment for an extended period, over a year, without the possibility of reinfection from the environment.     

Treatment of American cutaneous leishmaniasis with miltefosine, an oral agent.

There is no recognized oral treatment for American cutaneous leishmaniasis. A rising-dose, open-label phase I/II trial of the oral agent miltefosine against Colombian cutaneous leishmaniasis was conducted. Seventy-two male Colombian soldiers (mean weight, 67 kg) received miltefosine at 50-100 mg/day for 3 weeks (for 32 evaluable patients) or at 133-150 mg/day for 3-4 weeks (for 32 evaluable patients). The per-protocol cure rate for 50-100 mg/day was 21 (66%) of 32 patients. The per-protocol cure rate for 133-150 mg/day was 30 (94%) of 32 patients (P =.01, by use of Fisher's exact test). The historic per-protocol cure rate for standard injections of antimony is 93%. "Motion sickness" that did not interfere with normal duties was experienced by 40% of patients and was dose related. Vomiting and diarrhea were reported on approximately 2% of treatment days. In this uncontrolled study of oral miltefosine for treatment of patients with American cutaneous leishmaniasis, a dosage of approximately 2.25 mg/kg/day for 3-4 weeks was effective and tolerated.     

A randomized, double-blind, multicenter clinical trial on the efficacy of ivermectin against intestinal nematode infections in China

To assess the efficacy of ivermectin against intestinal nematode infections, a randomized, double-blind, multicenter clinical trial was carried out in a total of 816 human individuals infected with different nematodes from three counties in China. The subjects were randomly assigned into experimental and control groups and orally given a single dose of 0.1, 0.2, 0.2 and 0.2mg/kg ivermectin against Ascaris lumbricoides, hookworm, Trichuris trichiura and Enterobius vermicularis, respectively. Parallel control groups to each of the ivermectin groups were given a single oral dose of 6.7 mg/kg albendazole. The cure rates with ivermectin and albendazole were 100% (102/102) and 99.0% (101/102) for Ascaris, and 66.7% (68/102) and 67.7% (69/102) for Trichuris, respectively, with no significant difference (P>0.05) between the two treatments. The parasitological cure rates of albendazole were 69.6% (71/102) for hookworm and 94.1% (96/102) for Enterobius, which were significantly higher than ivermectin (33.3% and 52.9%, respectively, P<0.0001). The expulsion of worm in the feces reached its peak 1-2 days after ivermectin treatment. The study showed that ivermectin, with few side effects, could be used as an additional treatment tool for intestinal nematodes, especially for the treatment of Ascaris and Trichuris infections in China.     

日本血吸虫病与肠线虫病联合化疗的效果

血吸虫病人合并感染肠线虫者(A组)采取;吡喹酮40mg/kg加阿苯达唑200mg和复方甲苯咪唑400mg(尚含左旋咪唑100mg)分2d顿服,1个半月后血吸虫阴转率88.0％,蛔虫、鞭虫和钩虫阴转率分别为77.4％、23.6％及100.0％。对不合并血吸虫病的肠线虫病患者采取两种联合化疗方案:B组—阿苯达唑200mg和复方甲苯咪唑200mg(尚含左旋咪唑50mg)顿服,蛔虫、鞭虫和钩虫的阴转率分别为66.7％、18.8％和62.5％,较A组结果稍低;C组—阿苯达唑100mg和噻嘧啶900mg顿服的驱虫效果差,蛔虫和鞭虫的阴转率分别为50.0％及11.1％。3种驱虫方案对血吸虫和蛔虫的减卵率可达97.0％～99.9％;对钩虫的减卵率达68.9％～100％;对鞭虫的效果差。相应增加药物的剂量及改进服法,当可提高疗效。     

Comparison of high dose ivermectin and diethylcarbamazine for activity against bancroftian filariasis in Haiti

This three-phase study was designed to compare high dose ivermectin with a standard diethylcarbamazine (DEC) regimen for patient tolerability, potential to kill adult filaria, and duration of microfilarial suppression in 30 Haitian subjects with Wuchereria bancrofti microfilaremia. All were first given a 1-mg oral dose of ivermectin (phase 1) to reduce microfilaria densities. Participants were randomized into three groups: Group 1 received DEC (6mg/kg per day for 12 days), Group 2 received 200 mcg/kg of ivermectin, and Group 3 received 400 mcg/kg of ivermectin (200 mcg/kg per day for 2 days). All drug regimens were well tolerated with few adverse reactions. Most reactions occurred during phase I and consisted primarily of headache, fever, and myalgia. At the end of phase 1, 27 of 30 (90%) patients were microfilaria negative. During phase 2, four of the six men receiving DEC developed scrotal reactions suggesting killing adult worms; no such reactions were noted in 10 men receiving ivermectin (p less than 0.05). At one-year follow up (phase 3), all treatment groups had less than 10% return to pretreatment microfilaria levels. The mean percent of baseline microfilaria counts were for Group 1, 0.9% (range 0-5%); Group 2, 8.2% (range 0-31%); and Group 3, 3.8% (range 0-25%). Seven individuals in Group 1 were microfilaria-negative, while only one and three individuals were microfilaria-negative in Groups 2 and 3, respectively. These results suggest that DEC causes more damage to the adult worms and greater reduction in microfilaria densities than ivermectin, but that high doses of ivermectin may suppress microfilaremia in lymphatic filariasis for periods much longer than previously reported.     

Comparison of ivermectin and benzyl benzoate lotion for scabies in Nigerian patients

Few studies have compared ivermectin directly with topical agents in developing countries. We compared the effectiveness of oral ivermectin (200 microg/kg) with topical 25% benzyl benzoate and monosulfiram soap in 210 subjects of age 5 to 65 years with scabies. Subjects with persistent lesions after 2 weeks received a second course of treatment. All lesions had resolved after 2 weeks in 77 of 98 (79%) subjects treated with ivermectin and in 60 of 102 (59%) subjects treated topically (P = 0.003). The improvement in severity score was greater in the ivermectin group than in the topical treatment group (P < 0.001). The overall cure rate after 4 weeks was 95% in the ivermectin group and 86% in the topical treatment group (P = 0.04). Compared with topical benzyl benzoate and monosulfiram in the treatment of scabies, ivermectin was at least as effective and led to more rapid improvement.