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.     

Treatment of cutaneous gnathostomiasis with ivermectin

In a randomized open study, we compared the efficacy of a single dose of oral ivermectin (200 microg/kg) and oral albendazole (400 mg/day for 21 days) for the treatment of cutaneous gnathostomiasis. Thirty-one patients were randomly assigned to receive ivermectin (n = 17) or albendazole (n = 14). Thirteen of 17 patients who received ivermectin responded, 3 relapsed, and 1 was unresponsive (cure rate = 76%). Thirteen of 14 patients who received albendazole responded very well and did not relapse. Only one patient was unresponsive (cure rate = 92%; P > 0.05). No major side effects were observed in both groups. We concluded that a single dose of ivermectin (200 microg/kg) is less effective than albendazole (400 mg/day for 21 days) for treatment of cutaneous gnathostomiasis, but there was no statistically significant difference (P > 0.05).     

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.     

Ivermectin treatment of a traveler who returned from Peru with cutaneous gnathostomiasis.

We describe a 21-year-old patient who experienced a relapse of cutaneous gnathostomiasis after receiving initial treatment with albendazole and who had a successful outcome after receiving a short course of ivermectin for the relapse. This is the first reported case of gnathostomiasis acquired by a human in Peru.     

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.     

Prevalence of strongyloides in Northern Thailand and treatment with ivermectin vs albendazole

The stools of 697 cases were examined by agar plate technique at Tambon Makam Luang, Sun Pa Tong district, Chiang Mai; there were Strongyloides stercoralis 15.9%,Opisthorchis viverrini 5.1%, intestinal fluke 0.1%. Treatment with ivermectin 78 cases and albendazole 33 cases of strongyloidiasis gave cure rates at 98.7% and 78.7%, respectively. Alkaline phosphatase in some patients were increased at mild level after treatment. Side effects in ivermectin group were anorexia, nausia, diarrhea, diffuse itching and drowsiness; and in albendazole group were nausia and diarrhea. The efficacy of single dose and mild side effects suggest ivermectin as drug of choice for strongyloidiasis treatment.     

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.     

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.     

伊维菌素驱治肠道线虫的临床观察

目的观察伊维菌素驱治肠道线虫感染的效果及副作用。方法用伊维菌素0.1、0.2、0.2和0.2mg/kg顿服分别治疗蛔虫、钩虫、鞭虫和蛲虫感染者,并与阳性对照药阿苯达唑400mg顿服进行比较。结果随机双盲治疗,伊维菌素和阿苯达唑对蛔虫感染的虫卵阴转率均为100％(34/34),对钩虫感染的虫卵阴转率分别为17.6％(6/34)和76.5％(26/34),对鞭虫感染的虫卵阴转率分别为67.6％(23/34)和47.1％(16/34),对蛲虫感染的虫卵阴转率分别为58.8％(20/34)和100％(34/34)。服药后1～2d排虫达高峰。不良反应发生率低,血液学、肝肾功能和心电图检查无明显影响。结论伊维菌素治疗鞭虫感染疗效优于阿苯达唑,治疗蛔虫感染疗效与阿苯达唑相同,治疗钩虫、蛲虫感染疗效不及阿苯达唑。     

Assessment of combined ivermectin and albendazole for treatment of intestinal helminth and Wuchereria bancrofti infections in Haitian schoolchildren.

This randomized, placebo-controlled trial investigated the efficacy and nutritional benefit of combining chemotherapeutic treatment for intestinal helminths (albendazole) and lymphatic filariasis (ivermectin). Children were infected with Ascaris (29.2%), Trichuris (42.2%), and hookworm (6.9%), with 54.7% of children having one or more of these parasites. Wuchereria bancrofti microfilaria were found in 13.3% of the children. Children were randomly assigned to treatment with placebo, albendazole, ivermectin, or combined therapy. Combination treatment reduced the prevalence of Trichuris infections significantly more than either drug alone. Combination therapy also significantly reduced the prevalence and density of W. bancrofti microfilaremia compared with placebo or ivermectin alone. Only combination therapy resulted in significantly greater gains in height (hookworm-infected children) or weight (Trichuris-infected children) compared with the placebo group. Combined albendazole and ivermectin was a more efficacious treatment for intestinal helminth and W. bancrofti infections in children and resulted in nutritional benefits not found with either drug alone.     

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.     

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。     

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.     

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.     

伊维菌素和阿苯达唑伍用驱除肠道线虫感染的效果观察

目的 观察伊维菌素和阿苯达唑伍用治疗肠道线虫感染的效果。方法 采用国产伊维菌素伍用阿苯达唑(6mg+200mg)(14岁以下儿童剂量减半)分别治疗蛔虫、钩虫、鞭虫、蛲虫感染者,同时用阿苯达唑400mg治疗钩虫、鞭虫感染者、用伊维菌素12mg治疗钩虫、蛲虫感染者作为对照。结果 伊维菌素伍用阿苯达唑治疗蛔虫、钩虫、鞭虫、蛲虫感染者的虫卵阴转率分别为100.00％(30/30)、86.67％(26/30)、88.24％(30/34)和97.62％(41/42);阿苯达唑对照组钩虫和鞭虫的虫卵阴转率分别为70.58％(24/34)和47.06％(16/34),伊维菌素对照治疗组钩虫、蛲虫虫卵阴转率分别为46.15％(12/26)和57.14％(16/28)。伊维菌素伍用阿苯达唑的不良反应发生率低而轻,对血象、肝肾功能和心电图无明显影响。结论 国产伊维菌素伍用阿苯达唑治疗钩虫、鞭虫、蛲虫感染效果显著,对鞭虫疗效明显优于阿苯达唑,对钩虫、蛲虫疗效明显优于伊维菌素,并且有排虫快、不良反应少而轻等优点。     

伊维菌素治疗肠道线虫病的临床观察

目的观察伊维菌素驱治肠道线虫感染的效果及不良反应. 方法采用单剂国产伊维菌素12 mg、6 mg、12mg、12 mg(14岁以下儿童剂量减半)分别治疗钩、蛔、鞭、蛲虫感染者,同时用阿苯达唑400 mg治疗上述线虫感染者作为对照.结果伊维菌素和阿苯达唑对钩虫感染的虫卵阴转率分别为58.00%(29/50)和70.59%(24/34);对蛔虫感染的虫卵阴转率分别为100%(51/51)和97.06%(33/34);对鞭虫感染的虫卵阴转率分别为72.00%(36/50)和47.06%(16/34);对蛲虫感染的虫卵阴转率分别为56.86%(29/51)和91.18%(31/34).伊维菌素的不良反应发生率低而轻,对血象、肝肾功能和心电图无明显影响.结论伊维菌素6 mg治疗蛔虫感染效果显著,12 mg治疗鞭虫感染效果优于阿苯达唑400 mg,对钩虫和蛲虫感染亦有一定疗效,并且有排虫快、服药简便、不良反应少而轻等优点.     

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.     

Pharmacokinetics of azithromycin and the combination of ivermectin and albendazole when administered alone and concurrently in healthy volunteers

Azithromycin is a critical component of an integrated disease elimination program against trachoma. This study was conducted to evaluate whether azithromycin has a pharmacokinetic interaction with the combination of ivermectin and albendazole. Eighteen healthy volunteers were administered single doses of azithromycin, ivermectin/albendazole, and the combination of the three agents in random, crossover fashion. To assess the presence of interactions, test (combination) and reference (single dose) data were compared using an estimation approach. Compared with reference phases, the geometric mean values for the combination arm's azithromycin AUC(0-t) and C(max) were increased approximately 13% and 20%, respectively, albendazole AUC(0-t) decreased by approximately 3% and C(max) increased approximately 3%, and ivermectin AUC(0-t) and C(max) were increased 31% and 27%, respectively. Albendazole sulfoxide AUC(0-t) and C(max) were decreased approximately 16% and 14%, respectively. All treatments were well tolerated. The interactions for azithromycin and albendazole were minimal although the increase in ivermectin exposure requires further study.     

Effect of single-dose albendazole and single-dose mebendazole on Necator americanus

One hundred two children (43 males and 59 females) aged 6 to 14 years with positive stool examination by Kato-Katz and/or Harada-Mori culture techniques for N. americanus, were randomly divided into two groups. Group I with 48 children were treated with a single dose albendazole, 400 mg. Group II, 54 children, received a single dose mebendazole, 600 mg. After treatment, repeated stool examination was performed on Day 14, Day 21 and Day 28. The children were considered cured when stool examination was negative on all three occasions by both methods. The cure rate was 64% in Group I and 11% in Group II. The difference was statistically significant (p less than 0.05). The eggs reduction rate was 98% in Group I and 95% in Group II. Mild and transient side effects such as nausea, dizziness and headache were observed in both groups. Albendazole, 400 mg, as a single dose treatment was shown to be superior to mebendazole, 600 mg, single dose for the mass treatment of hookworm infection, especially that of Necator americanus, in an endemic area.     

Effects of a 3-day regimen of albendazole (800 mg daily) on Loa loa microfilaraemia

The encephalopathy that sometimes develops after ivermectin treatment in patients with high Loa microfilaraemias is probably related to a massive effect of the drug on the Loa microfilariae. A trial was therefore conducted to evaluate whether a course of albendazole would bring about a slower decrease in the Loa microfilaraemia, and thus could be used as a mass 'clearing' treatment, before the distribution of ivermectin in areas where onchocerciasis and loiasis are co-endemic. The Loa microfilarial loads were followed monthly for 9 months in two groups of subjects, one treated with albendazole (400 mg twice a day for 3 days), and the other with vitamin (B(1), B(6) and B(12)) tablets. There were no significant between-group differences in the microfilarial loads at any of the examination rounds. During the follow-up period, there was also no significant change in the overall loads among those treated with albendazole, although the counts in those with high initial microfilaraemias (>8000 microfilariae/ml) tended to decrease progressively during the first 3 months. Further trials should now be performed, to evaluate the effects on Loa loa of two courses of albendazole given 2-3 months apart.