Soil-transmitted helminths: A critical review of the impact of co-infections and implications for control and elimination

Abstract

Researchers have raised the possibility that soil-transmitted helminth (STH) infections might modify the host's immune response against other systemic infections. STH infections can alter the immune response towards type 2 immunity that could then affect the likelihood and severity of other illnesses. However, the importance of co-infections is not completely understood, and the impact and direction of their effects vary considerably by infection. This review synthesizes evidence regarding the relevance of STH co-infections, the potential mechanisms that explain their effects, and how they might affect control and elimination efforts. According to the literature reviewed, there are both positive and negative effects associated with STH infections on other diseases such as malaria, human immunodeficiency virus (HIV), tuberculosis, gestational anemia, pediatric anemia, neglected tropical diseases (NTDs) like lymphatic filariasis, onchocerciasis, schistosomiasis, and trachoma, as well as Coronavirus Disease 2019 (COVID-19) and human papillomavirus (HPV). Studies typically describe how STHs can affect the immune system and promote increased susceptibility, survival, and persistence of the infection in the host by causing a TH2-dominated immune response. The co-infection of STH with other diseases has important implications for the development of treatment and control strategies. Eliminating parasites from a human host can be more challenging because the TH2-dominated immune response induced by STH infection can suppress the TH1 immune response required to control other infections, resulting in an increased pathogen load and more severe disease. Preventive chemotherapy and treatment are currently the most common approaches used for the control of STH infections, but these approaches alone may not be adequate to achieve elimination goals. Based on the conclusions drawn from this review, integrated approaches that combine drug administration with water, sanitation and hygiene (WASH) interventions, hygiene education, community engagement, and vaccines are most likely to succeed in interrupting the transmission of STH co-infections. Gaining a better understanding of the behavior and relevance of STH co-infections in the context of elimination efforts is an important intermediate step toward reducing the associated burden of disease.

Fig 1. STHs employ both immune protection and immune suppression mechanisms to evade the host’s immune system.

The induction of type 2 immune response is thought to be a crucial immune protection mechanism, while the suppression of dendritic cell function and T cell activation are key immune suppression mechanisms. Helminths trigger the Th2 response that activates cells to release anti-inflammatory and regulatory cytokines (e.g., IL-4, IL-5, IL-9, IL-10, IL-13, TGF-B). These cytokines mediate the activation of effector mechanisms that include the antibody-based immune response and regulatory T cells, inhibit the proinflammatory Th1 response, and modulate antigen activity [–84]. Figure developed through www.biorender.com. STH, soil-transmitted helminth.

Fig 2. Integrated strategies for reducing the transmission of STH infections.

Created by authors. STH, soil-transmitted helminth.