The effect of helminth infection on vaccine responses in humans and animal models: A systematic review and meta‐analysis

Abstract

Vaccination has potential to eliminate infectious diseases. However, parasitic infections such as helminths may hinder vaccines from providing optimal protection. We reviewed existing literature on the effects of helminth infections and their treatment on vaccine responses in humans and animals. We searched literature until 31 January 2022 in Medline, EMBASE, Global health, Scopus, and Web of science; search terms included WHO licensed vaccines and human helminth types. Standardized mean differences (SMD) in vaccine responses between helminth infected and uninfected or anthelminthic treated and untreated individuals were obtained from each study with suitable data for meta‐analysis, and combined using a random effects model. Analysis was stratified by whether helminth exposure was direct or prenatal and by vaccine type. This study is registered with PROSPERO (CRD42019123074). Of the 4402 articles identified, 37 were included in the review of human studies and 24 for animal experiments. For human studies, regardless of vaccine type, overall SMD for helminth uninfected/treated, compared to infected/untreated, was 0.56 (95% CI 0.04–1.07 and I2 = 93.5%) for direct helminth exposure and 0.01 (95% CI −0.04 to 0.07 and I2 = 85.9%) for prenatal helminth exposure. Effects of anthelminthic treatment were inconsistent, with no overall benefit shown. Results differed by vaccine type, with responses to live vaccines most affected by helminth exposure. For animal studies, the most affected vaccine was BCG. This result indicates that helminth‐associated impairment of vaccine responses is more severe for direct, than for prenatal, helminth exposure. Further research is needed to ascertain whether deworming of individuals before vaccination may help improve responses.

A New Role for Old Friends: Effects of Helminth Infections on Vaccine Efficacy

“…Previous studies of other vaccines discussed in the preceding text suggest cause for concern on effects of helminth infections on COVID-19 vaccination programs. There is growing evidence that vaccine efficiency is reduced where helminth infections are prevalent, with reduced efficiencies shown for BCG, tetanus, diphtheria, measles, and malaria vaccines [ 13 ]. It has been reported helminths reduce Th1- and Th17-induced antiviral activity and vaccination efficacy [ 74 ].…”

“…Epidemiological surveys have found that mass vaccination is sometimes less effective than expected, especially in developing countries [ 7 , 8 ].The century-old Bacille Calmette-Guérin (BCG) and measles vaccines are reported to be less effective in Africa and Southeast Asia than in developed countries [ 9 , 10 ]. The failure of vaccination to achieve the desired protective effect is not only related to technical reasons, such as vaccine quality and vaccination method, but also related to environmental exposure, one of which is the prevalence of helminth infections in many regions around the world [ 11 , 12 , 13 , 14 ]. The World Health Organization (WHO) estimates that helminth infections affect more than a quarter of the population, and more than 880 million children require treatment for these parasite diseases, including approximately 350 million in the African region [ 15 ].…”

“…As our old friends of human coevolution, helminths and their metabolites and secretions interfere with immune responses to permit their persistence in hosts while dampening immune reactivity to bystander antigens in various immune disorders [ 12 ]. Some previous reviews have proved that the powerful immunomodulatory ability of helminth in hosts not only provides new avenues to treat immunological diseases such as allergies and autoimmunity, but also affects immunogenicity and efficacy of vaccines [ 12 , 13 , 22 ]. Given that helminth infections are among the most common infectious diseases in the world, evaluating vaccine efficiency affected by helminth infections may provide critical information for selecting optimal vaccination programs in regions with high parasite prevalence.…”

“…Given that helminth infections are among the most common infectious diseases in the world, evaluating vaccine efficiency affected by helminth infections may provide critical information for selecting optimal vaccination programs in regions with high parasite prevalence. The influence of helminth infections on vaccination has been previously reviewed, indicating that immune responses to vaccines are inhibited by the presence of helminth infections [ 12 , 13 , 22 , 23 , 24 ]. However, there is no systematic summary of the related immunological mechanism by which helminths affect vaccine effectiveness.…”

Unsupervised title and abstract screening for systematic review: a retrospective case-study using topic modelling methodology

“…To illustrate the utility of the proposed unsupervised title and abstract screening for systematic reviews, data from two completed systematic reviews will be used. A systematic review assessing the effect of helminths on vaccines response (Case study 1: the helminths data)a planned systematic review for which full-text review of documents has been completed [25] and from a published systematic review on the effectiveness of therapies for Wilson disease (Case study 2: Wilson disease data) [26] will be analysed. For both case studies, information on initial records identified through database search and results after manual title and abstract screening is available.…”