Presumptive treatment in immigrants from endemic areas
When unexplained eosinophilia is detected in any person who has migrated from an endemic area, screening for strongyloides infection is required. In the US, asymptomatic refugees who did not receive overseas presumptive ivermectin therapy for strongyloides may be presumptively treated upon arrival, or screened (using strongyloides IgG serology) if there are contraindications to presumptive treatment (e.g., concomitant Loa loa infection) or if ivermectin is unavailable.[37]Centers for Disease Control and Prevention. Presumptive treatment and screening for strongyloidiasis, infections caused by other soil-transmitted helminths, and schistosomiasis among newly arrived refugees. Mar 2021 [internet publication].
https://www.cdc.gov/immigrantrefugeehealth/guidelines/domestic/intestinal-parasites-domestic.html
Stool ova and parasite exam should not be used to rule out infection as it lacks sensitivity for Strongyloides infection. Refugees who have lived in Loa loa-endemic countries should be tested for Loa loa microfilariae before being treated with ivermectin in order to prevent complications including encephalopathy. Presumptive treatment for pregnant women is not recommended.[37]Centers for Disease Control and Prevention. Presumptive treatment and screening for strongyloidiasis, infections caused by other soil-transmitted helminths, and schistosomiasis among newly arrived refugees. Mar 2021 [internet publication].
https://www.cdc.gov/immigrantrefugeehealth/guidelines/domestic/intestinal-parasites-domestic.html
Risk of life-threatening hyperinfection is primarily related to immunosuppression, particularly the iatrogenic introduction of corticosteroid (or other immunosuppressive) therapy for a comorbid disorder.[20]Lim S, Katz K, Krajden S, et al. Complicated and fatal Strongyloides infection in Canadians: risk factors, diagnosis and management. CMAJ. 2004 Aug 31;171(5):479-84.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC514646
http://www.ncbi.nlm.nih.gov/pubmed/15337730?tool=bestpractice.com
[21]Newberry AM, Williams DN, Stauffer WM, et al. Strongyloides hyperinfection presenting as acute respiratory failure and gram-negative sepsis. Chest. 2005 Nov;128(5):3681-4.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1941746
http://www.ncbi.nlm.nih.gov/pubmed/16304332?tool=bestpractice.com
Empiric treatment with ivermectin is most likely necessary with iatrogenic immunosuppression, although serologic screening for infection can be pursued if time allows before immunosuppression commences. Presumptive treatment with ivermectin is recommended for people who have migrated from endemic areas and who require urgent corticosteroids for acute conditions (e.g., asthma), especially in the presence of eosinophilia.[11]Boulware DR, Stauffer WM, Hendel-Paterson BR, et al. Maltreatment of Strongyloides infection: case series and worldwide physicians-in-training survey. Am J Med. 2007 Jun;120(6):545.e1-8.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1950578
http://www.ncbi.nlm.nih.gov/pubmed/17524758?tool=bestpractice.com
For planned future immunosuppression, such as anticipated organ or bone marrow transplantation, screening should be performed as part of the pretransplant evaluation.
Initial therapy for confirmed infection
Ivermectin is considered the treatment of choice (regardless of resource setting) due to superior efficacy over albendazole.[1]World Gastroenterology Organisation. WGO practice guideline: management of strongyloidiasis. February 2018 [internet publication].
http://www.worldgastroenterology.org/assets/downloads/en/pdf/guidelines/15_management_strongyloidiasis_en.pdf
[38]Henriquez-Camacho C, Gotuzzo E, Echevarria J, et al. Ivermectin versus albendazole or thiabendazole for Strongyloides stercoralis infection. Cochrane Database Syst Rev. 2016 Jan 18;(1):CD007745.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4916931
http://www.ncbi.nlm.nih.gov/pubmed/26778150?tool=bestpractice.com
[
]
How does ivermectin compare with albendazole or thiabendazole for the treatment of Strongyloides stercoralis infection?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.1238/fullShow me the answer[Evidence B]5d279300-c292-46dd-8830-9e48c3746d74ccaBHow does ivermectin compare with albendazole for the treatment of Strongyloides stercoralis infection? A single dose of ivermectin is approximately 85% to 90% effective.[39]Suputtamongkol Y, Kungpanichkul N, Silpasakorn S, et al. 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 Jan;31(1):46-9.
http://www.ncbi.nlm.nih.gov/pubmed/18023151?tool=bestpractice.com
[40]Marti H, Haji HJ, Savioli L, 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 Nov;55(5):477-81.
http://www.ncbi.nlm.nih.gov/pubmed/8940976?tool=bestpractice.com
[41]Bisoffi Z, Buonfrate D, Angheben A, et al. Randomized clinical trial on ivermectin versus thiabendazole for the treatment of strongyloidiasis. PLoS Negl Trop Dis. 2011 Jul;5(7):e1254.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3144183
http://www.ncbi.nlm.nih.gov/pubmed/21814588?tool=bestpractice.com
Two doses are approximately 85% to 95% effective.[42]Nontasut P, Muennoo C, Sa-nguankiat S, et al. Prevalence of strongyloides in Northern Thailand and treatment with ivermectin vs albendazole. Southeast Asian J Trop Med Public Health. 2005 Mar;36(2):442-4.
http://www.ncbi.nlm.nih.gov/pubmed/15916052?tool=bestpractice.com
[43]Turner SA, Maclean JD, Fleckenstein L, et al. Parenteral administration of ivermectin in a patient with disseminated strongyloidiasis. Am J Trop Med Hyg. 2005 Nov;73(5):911-4.
http://www.ncbi.nlm.nih.gov/pubmed/16282302?tool=bestpractice.com
[44]Toma H, Sato Y, Shiroma Y, et al. Comparative studies on the efficacy of three anti-helminthics on treatment of human strongyloidiasis in Okinawa, Japan. Southeast Asian J Trop Med Public Health. 2000 Mar;31(1):147-51.
http://www.ncbi.nlm.nih.gov/pubmed/11023084?tool=bestpractice.com
[45]Suputtamongkol Y, Premasathian N, Bhumimuang K, et al. Efficacy and safety of single and double doses of ivermectin versus 7-day high dose albendazole for chronic strongyloidiasis. PLoS Negl Trop Dis. 2011 May 10;5(5):e1044.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091835
http://www.ncbi.nlm.nih.gov/pubmed/21572981?tool=bestpractice.com
[46]Buonfrate D, Salas-Coronas J, Muñoz J, et al. Multiple-dose versus single-dose ivermectin for Strongyloides stercoralis infection (Strong Treat 1 to 4): a multicentre, open-label, phase 3, randomised controlled superiority trial. Lancet Infect Dis. 2019 Nov;19(11):1181-90.
http://www.ncbi.nlm.nih.gov/pubmed/31558376?tool=bestpractice.com
Albendazole is considered a suitable alternative if ivermectin is not available, although the efficacy compared with ivermectin is very low.[1]World Gastroenterology Organisation. WGO practice guideline: management of strongyloidiasis. February 2018 [internet publication].
http://www.worldgastroenterology.org/assets/downloads/en/pdf/guidelines/15_management_strongyloidiasis_en.pdf
Thiabendazole is also recommended in countries where it is available, but it has a high rate of nausea (thiabendazole is no longer available in the US). Moxidectin is another possible alternative that has been approved in the US for onchocerciasis by the US Food and Drug Administration (FDA). It has a long history of use in veterinary medicine and may be used off-label for strongyloides. Moxidectin had a 94% cure rate for strongyloides in one randomized trial, which was similar to the 95% cure rate of ivermectin.[47]Barda B, Sayasone S, Phongluxa K, et al. Efficacy of moxidectin versus ivermectin against Strongyloides stercoralis infections: a randomized, controlled noninferiority trial. Clin Infect Dis. 2017 Jul 15;65(2):276-81.
https://academic.oup.com/cid/article/65/2/276/3090017
http://www.ncbi.nlm.nih.gov/pubmed/28369530?tool=bestpractice.com
As it has a long half life in tissue, a single dose is effective. It has not been studied in children aged <12 years. If ivermectin is unavailable, moxidectin may be the preferred alternative as albendazole is clearly inferior to ivermectin.
Anthelmintics are most effective against adult worms and are not very effective against migrating larvae. Thus, repeated therapy may be necessary to eradicate any residual strongyloides adults that have developed from migrating larvae in the interim.
Various treatment regimens exist and local guidance should be consulted. The US Centers for Disease Control and Prevention (CDC) recommends 1-2 doses of ivermectin administered on consecutive days.[36]Centers for Disease Control and Prevention. Parasites - strongyloides: resources for health professionals. Mar 2023 [internet publication].
https://www.cdc.gov/parasites/strongyloides/health_professionals/index.html#tx
However, some regimens recommend the second dose to be given 2 weeks after the first dose, regardless. The efficacy of one dose of ivermectin has been directly compared with two doses separated by 2 weeks in a randomized trial without any difference found.[46]Buonfrate D, Salas-Coronas J, Muñoz J, et al. Multiple-dose versus single-dose ivermectin for Strongyloides stercoralis infection (Strong Treat 1 to 4): a multicentre, open-label, phase 3, randomised controlled superiority trial. Lancet Infect Dis. 2019 Nov;19(11):1181-90.
http://www.ncbi.nlm.nih.gov/pubmed/31558376?tool=bestpractice.com
Ivermectin may very rarely precipitate encephalitis in people who have concomitant heavy infection with Loa loa, due to the mass killing of microfilariae in the central nervous system. This is becoming more of a theoretical concern due to the success of the ongoing river blindness (onchocerciasis) eradication programs led by the Carter Center, which use ivermectin. However, should current eradication programs break down (e.g., in situations such as long-term war), people should then be screened for filariasis by blood smear collected between 10 a.m. and 2 p.m., before receiving ivermectin.[28]Esum M, Wanji S, Tendongfor N, et al. Co-endemicity of loiasis and onchocerciasis in the South West Province of Cameroon: implications for mass treatment with ivermectin. Trans R Soc Trop Med Hyg. 2001 Nov-Dec;95(6):673-6.
http://www.ncbi.nlm.nih.gov/pubmed/11816443?tool=bestpractice.com
In critically ill people with hyperinfection or disseminated strongyloidiasis unable to take oral medications, ivermectin has been administered successfully by subcutaneous, intravenous, or rectal routes. No FDA-approved formulations for these routes of administration are available for any of the strongyloides therapy options. However, veterinary formulations of ivermectin are available for subcutaneous, intravenous, and rectal use, and have been used successfully in life-threatening hyperinfection. For critically ill people, ivermectin is given daily for a duration of 7-14 days. Alternatively, ivermectin and albendazole have been administered together for this indication.[48]Pornsuriyasak P, Niticharoenpong K, Sakapibunnan A. Disseminated strongyloidiasis successfully treated with extended duration ivermectin combined with albendazole: a case report of intractable strongyloidiasis. Southeast Asian J Trop Med Public Health. 2004 Sep;35(3):531-4.
http://www.ncbi.nlm.nih.gov/pubmed/15689061?tool=bestpractice.com
Involvement of a tropical medicine specialist is recommended.
If the patient is pregnant, the risks and benefits of treatment should be carefully considered. In chronic strongyloides infection, deferring treatment until after pregnancy is reasonable; however, in hyperinfection or disseminated strongyloidiasis, therapy should be given immediately. Data on ivermectin and albendazole use in pregnancy is sparse, but no increased teratogenicity has been reported with inadvertent use in the first trimester during lymphatic filariasis eradication programs.[49]Gyapong JO, Chinbuah MA, Gyapong M. Inadvertent exposure of pregnant women to ivermectin and albendazole during mass drug administration for lymphatic filariasis. Trop Med Int Health. 2003 Dec;8(12):1093-101.
http://www.ncbi.nlm.nih.gov/pubmed/14641844?tool=bestpractice.com
Specialist advice should be sought if corticosteroids are required to accelerate fetal lung development. Treatment should be supervised by a tropical medicine specialist.
Children are treated with the same medications as adults. The safety of ivermectin in children who weigh <15 kg has not been determined; however, mass prevention campaigns recommend its use in children who are ≥90 cm tall, and in children aged <3 years at a reduced dose. Albendazole has been used in children as young as 1 year old in mass prevention campaigns.[36]Centers for Disease Control and Prevention. Parasites - strongyloides: resources for health professionals. Mar 2023 [internet publication].
https://www.cdc.gov/parasites/strongyloides/health_professionals/index.html#tx
Generally, children tolerate treatment better than adults. Of note, these drugs are unavailable as a suspension or syrup but tablets can be crushed.
Poor response to initial therapy
People not completing a treatment course, whether due to intolerance, noncompliance, or other reasons, should be given retreatment. Two doses of ivermectin are generally well-tolerated.
Treatment failure is the most probable cause of eosinophilia persisting beyond 4-6 months after treatment.[11]Boulware DR, Stauffer WM, Hendel-Paterson BR, et al. Maltreatment of Strongyloides infection: case series and worldwide physicians-in-training survey. Am J Med. 2007 Jun;120(6):545.e1-8.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1950578
http://www.ncbi.nlm.nih.gov/pubmed/17524758?tool=bestpractice.com
[33]Loutfy MR, Wilson M, Keystone JS, et al. Serology and eosinophil count in the diagnosis and management of strongyloidiasis in a non-endemic area. Am J Trop Med Hyg. 2002 Jun;66(6):749-52.
http://www.ncbi.nlm.nih.gov/pubmed/12224585?tool=bestpractice.com
Persistent eosinophilia requires retreatment with ivermectin and consideration of screening for human T-cell lymphotropic virus type-1 (HTLV-1) infection.[23]Zaha O, Hirata T, Uchima N, et al. Comparison of anthelmintic effects of two doses of ivermectin on intestinal strongyloidiasis in patients negative or positive for anti-HTLV-1 antibody. J Infect Chemother. 2004 Dec;10(6):348-51.
http://www.ncbi.nlm.nih.gov/pubmed/15614460?tool=bestpractice.com
In immunosuppressed people, such as those with HTLV-1 infection or HIV/AIDS, multiple 14-day treatment courses may be necessary, separated by 2-week intervals. Follow-up stool ova and parasite exams verify eradication of strongyloides at 3 and 6 months. Alternatively, serology could be followed.[50]Biggs BA, Caruana S, Mihrshahi S, et al. Management of chronic strongyloidiasis in immigrants and refugees: is serologic testing useful? Am J Trop Med Hyg. 2009 May;80(5):788-91.
http://www.ncbi.nlm.nih.gov/pubmed/19407125?tool=bestpractice.com
In 65% to 80% of people, the quantitative serology will decrease by 40% or become negative after 6 months.[51]Kobayashi J, Sato Y, Toma H, et al. Application of enzyme immunoassay for postchemotherapy evaluation of human strongyloidiasis. Diagn Microbiol Infect Dis. 1994 Jan;18(1):19-23.
http://www.ncbi.nlm.nih.gov/pubmed/8026153?tool=bestpractice.com
Less than 40% decrease in quantitative serology after 6 months, or an increase in titer, prompts retreatment.[52]Salvador F, Sulleiro E, Sánchez-Montalvá A, et al. Usefulness of strongyloides stercoralis serology in the management of patients with eosinophilia. Am J Trop Med Hyg. 2014 May;90(5):830-4.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015573
http://www.ncbi.nlm.nih.gov/pubmed/24615124?tool=bestpractice.com