Helminth therapy (worms) for allergic rhinitis

Abstract

Allergic rhinitis is a disorder of the nasal membranes and surrounding tissues, and a worldwide cause of illness and disability. Helminths are complex tissue-dwelling or lumen-dwelling organisms that inhabit larger organisms and are frequently asymptomatic. Helminths modulate the natural immune responses of their human hosts, and may prevent or cure immune-mediated or allergic diseases (e.g. allergic rhinitis) in the host. Non-randomised studies support this hypothesis. To assess the safety and effectiveness of helminth therapy in people with allergic rhinitis. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 24 June 2011. All randomised controlled trials where the intervention was any helminth species or combination of helminth species, administered to people with allergic rhinitis in any dose, by any route and for any duration of exposure. We accepted both intermittent and persistent allergic rhinitis patients. We independently extracted data and assessed eligibility and risk of bias using a standardised data collection form. We resolved any disagreement through discussion. We combined dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), presenting both with 95% confidence intervals (CI). We found five reports of two single-centre, placebo-controlled, double-blinded studies (130 participants). Participants in both studies were a mix of adults with either intermittent or persistent allergic rhinitis. Both studies had a low risk of bias. One study, with 12 weeks' follow-up, used a single percutaneous application of 10 Necator americanus (i.e. human hookworm) larvae. The other study, with 24 weeks' follow-up, used three-weekly oral dosing with 2500 Trichuris suis (i.e. pig whipworm) eggs in aqueous suspension. Of 17 outcomes evaluated in this review, eight were positive (i.e. favoured helminths). Participants taking helminths had no reduction in allergic rhinitis symptoms, percentage of well days (i.e. days with minimal symptoms and no use of medication for allergic rhinitis), lung function measures and quality of life scores. Total use of medication for allergic rhinitis (eye drops, nasal sprays, tablets) did not change; however, in the helminth group there was a statistically significant reduction in the percentage of days during the grass pollen season when participants needed to take tablets as rescue medication for their allergic rhinitis symptoms (MD -14.0%, 95% CI -26.6 to -1.40); in a typical 60-day pollen season this 14% reduction translates into 19 days when tablets would be needed in the helminth group versus 27 days when tablets would be needed in the placebo group.Participants taking helminths percutaneously (i.e. as hookworm larvae) had local skin itching and redness in the first few days after administration. Participants taking helminths were more likely to report any gastrointestinal adverse event (RR 1.79, 95% CI 1.31 to 2.45), moderate or severe abdominal pain (RR 7.67, 95% CI 1.87 to 31.57), moderate or severe flatulence (RR 2.01, 95% CI 1.06 to 3.81) and moderate or severe diarrhoea (RR 1.99, 95% CI 1.18 to 3.37). There was no difference between the helminth and placebo groups in the incidence of serious adverse events, and in study withdrawals. There is currently insufficient evidence on the efficacy, tolerability and likely costs of helminth therapy to support its use in the routine management of allergic rhinitis. Administered to humans in carefully measured doses, helminths appear to be safe. More preclinical studies should be performed, before larger and extended duration trials of helminths for allergic rhinitis are carried out. Future studies should collect and report comparative data on the costs of helminth therapy versus conventional pharmacotherapy.