Efficacy and safety of single and double doses of ivermectin versus 7-day high dose albendazole for chronic strongyloidiasis

Yupin Suputtamongkol, Nalinee Premasathian, Kid Bhumimuang, Duangdao Waywa, Surasak Nilganuwong, Ekkapun Karuphong, Thanomsak Anekthananon, Darawan Wanachiwanawin, Saowaluk Silpasakorn, Yupin Suputtamongkol, Nalinee Premasathian, Kid Bhumimuang, Duangdao Waywa, Surasak Nilganuwong, Ekkapun Karuphong, Thanomsak Anekthananon, Darawan Wanachiwanawin, Saowaluk Silpasakorn

Abstract

Background: Strongyloidiasis, caused by an intestinal helminth Strongyloides stercoralis, is common throughout the tropics. It remains an important health problem due to autoinfection, which may result in hyperinfection and disseminated infection in immunosuppressed patients, especially patients receiving chemotherapy or corticosteroid treatment. Ivermectin and albendazole are effective against strongyloidiasis. However, the efficacy and the most effective dosing regimen are to be determined.

Methods: A prospective, randomized, open study was conducted in which a 7-day course of oral albendazole 800 mg daily was compared with a single dose (200 microgram/kilogram body weight), or double doses, given 2 weeks apart, of ivermectin in Thai patients with chronic strongyloidiasis. Patients were followed-up with 2 weeks after initiation of treatment, then 1 month, 3 months, 6 months, 9 months, and 1 year after treatment. Combination of direct microscopic examination of fecal smear, formol-ether concentration method, and modified Koga agar plate culture were used to detect strongyloides larvae in two consecutive fecal samples in each follow-up visit. The primary endpoint was clearance of strongyloides larvae from feces after treatment and at one year follow-up.

Results: Ninety patients were included in the analysis (30, 31 and 29 patients in albendazole, single dose, and double doses ivermectin group, respectively). All except one patient in this study had at least one concomitant disease. Diabetes mellitus, systemic lupus erythrematosus, nephrotic syndrome, hematologic malignancy, solid tumor and human immunodeficiency virus infection were common concomitant diseases in these patients. The median (range) duration of follow-up were 19 (2-76) weeks in albendazole group, 39 (2-74) weeks in single dose ivermectin group, and 26 (2-74) weeks in double doses ivermectin group. Parasitological cure rate were 63.3%, 96.8% and 93.1% in albendazole, single dose oral ivermectin, and double doses of oral ivermectin respectively (P = 0.006) in modified intention to treat analysis. No serious adverse event associated with treatment was found in any of the groups.

Conclusion/significance: This study confirms that both a single, and a double dose of oral ivermectin taken two weeks apart, is more effective than a 7-day course of high dose albendazole for patients with chronic infection due to S. stercoralis. Double dose of ivermectin, taken two weeks apart, might be more effective than a single dose in patients with concomitant illness.

Trial registration: ClinicalTrials.gov NCT00765024.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1. Total number of enrollment, randomization,…
Figure 1. Total number of enrollment, randomization, follow-up, and inclusion in the final analysis comparing among three treatment groups.
Figure 2. Kaplan-Meier Plot comparing the parasitological…
Figure 2. Kaplan-Meier Plot comparing the parasitological cure among the albendazole, ivermectin-I, and ivermectin-II treatment groups over one year follow-up period.

References

    1. Bethony J, Brooker S, Albonico M, Geiger SM, Loukas A, et al. Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm. Lancet. 2006;367:1521–1532.
    1. Sithithaworn P, Srisawangwong T, Tesana S, Daenseekaew W, Sithithaworn J, et al. Epidemiology of Strongyloides stercoralis in north-east Thailand: application of the agar plate culture technique compared with the enzyme-linked immunosorbent assay. Trans R Soc Trop Med Hyg. 2003;97:398–402.
    1. Concha R, Harrington W, Rogers AI. Intestinal strongyloidiasis: recognition, management, and determinants of outcomes. J Clin Gastroenterol. 2005;39:203–211.
    1. Hirata T, Uchima N, Kishimoto K, Zaha O, Kinjo N, et al. Impairment of host immune response against Strongyloides stercoralis by human T cell lymphotropic virus type 1 infection. Am J Trop Med Hyg. 2006;74:246–9.
    1. Keiser PB, Nutman TB. Strongyloides stercoralis in the immunocompromised population. Clin Microbiol Rev. 2004;17:208–17.
    1. Roxby AC, Gottlieb GS, Limaye AP. Strongyloidiasis in transplant patients. Clin Infect Dis. 2009;49:1411–1423.
    1. Seybolt LM, Christiansen D, Barnett ED. Diagnostic evaluation of newly arrived asymptomatic refugees with eosinophilia. Clin Infect Dis. 2006;42:363–367.
    1. Siddiqui AA, Berk SL. Diagnosis of Strongyloides stercoralis infection. Clin Infect Dis. 2001;33:1040–1047.
    1. Ebrahim A, El-Morshedy H, Omer E, El-Daly S, Barakat R. Evaluation of the Kato-Katz thick smear and formol ether sedimentation techniques for quantitative diagnosis of Schistosoma mansoni infection. Am J Trop Med Hyg. 1997;57:706–708.
    1. Koga K, Kasuya S, Khamboonruang C, Sukhavat K, Ieda M, et al. A modified agar plate method for detection of Strongyloides stercoralis. Am J Trop Med Hyg. 1991;45:518–521.
    1. Knopp S, Mgeni AF, Khamis IS, Steinmann P, Stothard JR, et al. Diagnosis of Soil-Transmitted Helminths in the Era of Preventive Chemotherapy: Effect of Multiple Stool Sampling and Use of Different Diagnostic Techniques. PLoS Negl Trop Dis. 2008;2(11):e331. :10.1371/journal.pntd.0000331.
    1. Rossignol JF, Maisonneuve H. Albendazole: placebo controlled study in 870 patients with intestinal helminthiasis. Trans R Soc Trop Med Hyg. 1983;77:707–711.
    1. Pungpak S, Bunnag D, Chindanond D, Radmoyos B. Albendazole in the treatment of strongyloidiasis. Southeast Asian J Trop Med Public Health. 1987;18:207–210.
    1. Archibald LK, Beeching NJ, Gill GV, Bailey JW, Bell DR. Albendazole is effective treatment for chronic strongyloidiasis. Q J Med. 1993;86:191–195.
    1. Pitisuttithum P, Supanaranond W, Chindanond DA. Randomized comparative study of albendazole and thiabendazole in chronic strongyloidiasis. Southeast Asian J Trop Med Public Health. 1995;26:735–738.
    1. Gann PH, Neva FA, Gam AA. A randomized trial of single- and two-dose ivermectin versus thiabendazole for treatment of strongyloidiasis. J Infect Dis. 1994;169:1076–1079.
    1. Datry A, Hilmarsdottir I, Mayorga-Sagastume R, Lyagoubi M, Gaxotte P, et al. Treatment of Strongyloides stercoralis infection with ivermectin compared with albendazole: results of an open study of 60 cases. Trans R Soc Trop Med Hyg. 1994;89:344–345.
    1. Marti H, Haji HJ, Savioli L, Chwaya HM, Mgeni AF, et al. A comparative trial of a single-dose ivermectin versus three days of albendazole for treatment of Strongyloides stercoralis and other soil-transmitted helminth infections in children. Am J Trop Med Hyg. 1996;55:477–481.
    1. Toma H, Sato Y, Shiroma Y, Kobayashi J, Shimabukuro I, et al. Comparative studies on the efficacy of three anthelminthics on treatment of human strongyloidiasis in Okinawa, Japan. Southeast Asian J Trop Med Public Health. 2000;31:147–151.
    1. Nontasut P, Muennoo C, Sa-nguankiat S, Fongsri S, Vichit A. Prevalence of Strongyloides in northern Thailand and treatment with ivermectin vs albendazole. Southeast Asian J Trop Med Public Health. 2005;36:442–444.
    1. Suputtamongkol Y, Kungpanichkul N, Silpasakorn S, Beeching NJ. Efficacy and safety of a single-dose veterinary preparation of ivermectin versus 7- day high-dose albendazole for chronic strongyloidiasis. Int J Antimicrob Agents. 2008;31:46–49.
    1. Zaha O, Hirata T, Kinjo F, Saito A, Fukuhara H. Efficacy of ivermectin for chronic strongyloidiasis: two single doses given 2 weeks apart. J Infect Chemother. 2002;8:94–98.

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