Abstract: 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.

Plain-language summary: We included two well-designed studies with a total of 130 adult participants, each study using a different species of gastrointestinal helminth (human hookworm in one study and pig whipworm in the other) as the intervention. Both studies found no significant efficacy from helminths, although one helminth species (Trichuris suis, the pig whipworm) reduced the need for participants to take tablets as ‘rescue medication’ during the grass pollen season. Adverse events such as abdominal pain and flatulence were commoner in the helminth group, but the two helminths species studied did not cause serious adverse reactions. Currently there is insufficient evidence to support the use of helminths for allergic rhinitis in routine clinical practice. More preclinical studies are needed, before larger and extended duration clinical trials of helminths for allergic rhinitis are performed.