Resolution of eosinophilia after treatment of cutaneous gnathostomiasis.

The present study was to investigate the dynamics of eosinophil in peripheral blood of patients with cutaneous gnathostomiasis before and after worm removal. The total of 28 proven cases of cutaneous gnathostomiasis treated by albendazole were included in the present study. The absolute eosinophil count (AEC) was higher than 500/ul during infestation in almost all the patients, the positive rate was 89%, and significantly decreased to normal level after receiving albendazole and worm removal within 3 months in 96%. In conclusion, an increas of AEC is another important hallmarks of cutaneous gnathostomiasis and this parameter could be the earlier indicator for responsiveness to treatment.

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.

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.

Lack of efficacy of quinine and artemether against advanced third-stage larvae of Gnathostoma spinigerum in vitro.

The efficacy of quinine and artemether--the effective blood schizontocide in malarial treatment--has been in vitro tested with the advanced third-stage larvae of Gnathostoma spinigerum. All larvae were collected from freshwater eel (Fluta alba) and exposed to the culture medium, each containing either quinine dihydrochloride or artemether at a final concentration of 20 microg/ml and 0.5 microg/ml, respectively for 21 consecutive days. Larval motility was assessed daily and the topographical changes were assessed using scanning electron microscope after 21-days of drug exposure. All worms moved actively for 21 days of study period and no change in surface ultrastructure was observed. Quinine and artemether at these concentrations have no effect on movement and topographical changes on the advanced third-stage larvae of this parasite.

Scanning electron microscopic observations on advanced third-stage larva of Gnathostoma spinigerum after in vitro exposure to albendazole sulphoxide.

Gnathostomiasis is the parasitic disease caused by the migration of an advanced third-stage larva of Gnathostoma spinigerum. To date, albendazole is claimed to be the effective drug in preventing the reoccurrence of migratory swelling in patients. After being exposed to 1 and 2 micrograms/ml albendazole sulphoxide (AlbSO) in vitro, the parasites moved deteriorately, however, no dead larva was found even exposed to these concentrations for 21 consecutive days. The topographical alterations after 21 days of albendazole sulphoxide exposure are described using a scanning electron microscope. The marked changes in surface morphology were observed in both neck and body regions. The tegumental surface on the neck region was swollen and covered with fuzzy materials, whereas, the spines on the posterior region of the body were dislodged. These changes would probably lead to reduction of intermittent cutaneous migratory swelling in human gnathostomiasis patients.

Movability of advanced third-stage larva of Gnathostoma spinigerum exposed to albendazole sulphoxide in vitro.

Movability of advanced third-stage larvae of Gnathostoma spinigerum exposed to albendazole sulphoxide (AlbSO), the active metabolite of albendazole, was determined in vitro. Larvae in control groups moved actively with the whole body for all 21 days of the study period. In larvae treated with AlbSO 1 microg/ml, the movement was significantly reduced after 11 days exposed to the drug and to be only a part of body on the 15th-21st days. In larvae treated with AlbSO 2 microg/ml, the movement was initiated in decreasing after 9th days and to be only a part of body on the 12th-17th days. Finally, worms were immobile but not dead on the 20th-21st days. Although there was no larvae died at 21st days exposed to AlbSO in both concentrations; but all worms were sluggish and may die later. These lethargic worms may not be able to migrate in patients and leading to cure. Albendazole may not be benefit for acute symptom clearance; however, it can prevent the recurrent migratory swelling after the treatment of 21 day-course.

Albendazole stimulates outward migration of Gnathostoma spinigerum to the dermis in man.

Human gnathostomiasis is characterized by space-occupying inflammatory lesions and/or hemorrhage as a result of the migration of, very often, a single larva of Gnathostoma spinigerum. Intermittent cutaneous migratory swellings occurring over years is the most common manifestation and the rare cerebral invasion may be fatal. There are currently no effective anthelminthics for this infection. During a double-blind randomized placebo control trial evaluating the efficacy of albendazole in cutaneous gnathostomiasis at a dosage of 400 mg twice daily for two weeks, it was observed that gnathostome larvae tended to migrate outward as a result of the treatment so that they could be recovered by excisional biopsy or by picking with a needle. In the placebo-treated group (N = 40), no such migration was observed during the 8,470 patient-days of follow-up while in the albendazole-treated group (N = 41) there was one worm in an excisional biopsy done on day 16 and two worms were removed from the skin by the patients themselves on days 8 and 0. Assuming that the period of drug exposure of the gnathostomes was the 14 days of albendazole administration plus another washout period of 7 days (equivalent to 20 half-lives of the active detectable metabolite), the total patient-days of albendazole exposure was 830. The rate of outward migration of gnathostomes in the drug treated group (3 per 830 patient-days) was significantly (p < 0.0001) higher than in the placebo group (0 per 8,470 patient-days).(ABSTRACT TRUNCATED AT 250 WORDS)