Helminth infections are among the neglected tropical diseases affecting billions of people globally, predominantly in developing countries. Helminths’ effects are augmented by coincident tuberculosis disease, which infects a third of the world’s population. The role of helminth infections on the pathogenesis and pathology of active tuberculosis (T.B.) remains controversial. Parasite-induced suppression of the efficacy of Bacille Calmette-Guerin (BCG) has been widely reported in helminth-endemic areas worldwide. T.B. immune response is predominantly proinflammatory T-helper type 1 (Th1)-dependent. On the other hand, helminth infections induce an opposing anti-inflammatory Th2 and Th3 immune-regulatory response.
References | Study Type, Location and Helminth(s) | Study Aim | Major Findings |
---|---|---|---|
[72][44] | Human study in Kenya. Wuchereria bancrofti and Schistosoma haematobium |
To investigate whether prenatal immunity to helminths persists in childhood and if it alters the immune response to BCG | Compared to patients who had prenatal sensitization 10–14 months after BCG immunization, T cell IFN-γ production was 26-fold higher in infants who were not sensitized to filariae or schistosomes in utero. |
[73][45] | Human study in South Africa. Ascaris lumbricoides and Trichuris trichiura |
To determine total serum IgE before and after tuberculosis therapy | T.B. therapy resulted in reduced serum Ascaris-specific IgE levels. Tuberculin induration was found to be inversely related to IgE in patients but not in controls. |
[65][37] | Human study in West Cameroon. Onchocerca volvulus |
To determine total serum IgE before and after tuberculosis therapy | T.B. therapy resulted in reduced serum Ascaris-specific IgE levels. Tuberculin induration was found to be inversely related to IgE in patients but not in controls. |
[64][36] | Human study in East Ethiopia. Ascaris lumbricoides, hookworms, Trichuris trichiura, Strongyloides stercoralis, Hymenolepis nana and Taenia spp. |
To investigate the effect of intestinal helminths on the immune response to PPD in naturally immunized or BCG-vaccinated individuals | Individuals who received BCG vaccination and were infected with helminths had reduced T cell and PPD skin test responses. Increased T cell proliferation and IFN were associated with improved BCG efficacy following anthelmintic therapy. |
[66][38] | An experimental study in Ethiopia. Schistosoma mansoni |
To investigate whether chronic helminth-infected individuals have reduced efficacy of BCG vaccine compared to uninfected persons | Possibly through attenuation of protective immune responses to mycobacterial antigens and/or by polarizing the general immune responses to the Th2 profile, S. mansoni infection reduced the protective efficacy of BCG vaccination against Mtb. |
[53][23] | Human study in Ethiopia. Ascaris lumbricoides, Hookworm, Strongloides stercoralis, Trichuris trichiura, S. mansoni and Enterobius vermicularis |
To study the prevalence of intestinal helminth infections and their association with active T.B. in T.B. patients and healthy household contacts | In addition to HIV infection, intestinal helminth infection may be a risk factor for the development of active pulmonary T.B. This discovery could have significant consequences for the control of tuberculosis in helminth-endemic areas around the world. |
[30][24] | Human study in Ethiopia. Trichuris trichiura, Ascaris lumbricoides, hookworms, Taenia spp., Hymenolepis nana and Enterobius vermicularis |
This study tested anti-helminthic medication before BCG vaccination to determine if it could improve BCG vaccination immunogenicity in helminth-infected patients | Chronic worm infection reduced BCG immunogenicity in humans. This was linked to increased TGF-β production but not a better Th2 immune response. |
[74][46] | Human study in South Africa. Ascaris lumbricoides and Trichuris trichiura |
To investigate whether helminth infection could affect a child’s ability to generate a proper Th1 immune response, which was defined by a positive tuberculin skin test (TST) | Helminth infection/exposure may reduce the immune response to Mtb infection. In younger children, being Ascaris IgE-positive significantly reduced the likelihood of being TST-positive, but this effect faded as they grew older. |
[75][47] | Human study in Venezuela. Ascaris lumbricoides and Trichuris trichiura |
To investigate the effects of parasite infections, malnutrition and plasma cytokine profiles on tuberculin skin test (TST) positivity | TST positivity was associated with low plasma Th1 cytokine levels in indigenous Venezuelan children with T.B. contacts and helminth infections. |
[19] | Animal study in South Africa. Nippostrongylus brasiliensis (Nb) |
To investigate the impact of acute Nb-induced lung damage and long-term parasite lung conditioning on the host’s ability to control mycobacterial infection | The findings show that early stage Nb infection induces a macrophage response that protects against subsequent mycobacterial infection. |
[76][48] | Human study in Ethiopia. Giardia lamblia, Ascaris lumbricoides, Hookworm spp., Strongyloides stercoralis, Trichuris trichuria, Enterobius vermicularis, Taenia spp., Hymenolepis nana, Schistosoma mansoni or trophozoite stage of Entamoeba histolytica. |
To diagnose latent Mtb infection using the tuberculin skin test (TST) and the IFN-γ release assays in helminth infected school children | The tuberculin skin test should be used with caution in areas where parasitic intestinal infections are common. |
[77][49] | Human study in Uganda. Hookworm, Trichuris trichiura, Hymenolepis nana, Schistosoma mansoni, Ascaris lumbricoides, Hymenolepis nana and Schistosoma mansoni |
To determine whether coinfections such as helminths, malaria and HIV modulate the immune system and increase susceptibility to latent tuberculosis infection (LTBI), leading to the persistence of the tuberculosis epidemic | Concurrent helminth, malaria and HIV infections did not affect cytokine responses profile in individuals with LTBI. |
[78][50] | Human study in Ethiopia. Schistosoma mansoni |
To investigate whether maternal helminth infection affects maternal and neonatal immunological function and T.B. immunity | The combination of early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) elicited a significantly lower IFN-γ response in helminth-positive than in helminth-negative participants. Cord blood mononuclear cells’ (CBMCs) IFN-γ response, total IgE and cross-placental transfer of T.B.-specific IgG were all negatively correlated with maternal helminth infection. |
[17] | Human study in Ethiopia. Ascaris lumbricoides Hookworm spp. Strongyloides stercoralis Trichuris trichiura Hymenolepis nana Taenia spp. |
To examine the clinical and immunological effects of helminth infection on T.B. | Asymptomatic helminth infection had a profound influence on the immunological profile of individuals with T.B. This favored Th2 immune responses such as increased regulatory T cells and IL-5 and IL-10 secreting cells. |
[79][51] | Human study in Ethiopia. Ascaris lumbricoides |
To investigate the clinical and immunological outcomes of patients coinfected with helminths and T.B. after albendazole treatment | The decrease in eosinophil counts and IL-10 demonstrated that asymptomatic helminth infection considerably impacts host immunity during tuberculosis and can be efficiently reversed with albendazole treatment. Helminth infection has clinical effects on chronic infectious diseases such as tuberculosis, and these effects should be further explored. |
[80][52] | An animal study in the USA. Schistosoma mansoni |
To investigate whether Mtb-specific T cell responses can be reversibly impaired by treatment of S. mansoni coinfection, without impacting arginase-1-expressing macrophage-mediated T.B. control | Anthelminthic treatment improved Mtb-specific T cell responses. In T.B.-infected mice, arginase-1-expressing macrophages in the lung formed granulomas and exacerbated inflammation. |
[81][53] | An experimental animal study in USA. Heligmosomoides polygyrus |
To investigate whether Mtb infection would be modulated in mice with chronic H. polygyrus infection | Despite a systemic increase in FoxP3+ T regulatory cells, neither primary nor memory immunity conferred by Mycobacterium bovis BCG vaccination were affected in mice with chronic enteric helminth infection. |
[82][54] | Human study in India. Strongyloides stercoralis |
To investigate whether helminth modulation of cytokine responses in latent T.B. coinfection is reversible after anthelminthic therapy | In Strongyloides stercoralis-latent T.B. coinfection, anthelmintic therapy reversed the modulation of systematic and T.B. antigen-stimulated cytokine responses. |