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Mbani Mpega Ntigui CN, Oyegue-Liabagui SL, Mouloungui-Mavoungou J, Ndjangangoye NK, Madoungou Idoumi DL, Kouna LC, Kassa Kassa RF, Moukodoum ND, Ontoua SS, Imboumy Limoukou RK, Biteghe Bi Essone JC, Okouga AP, Bagueboussa F, Lekana-Douki JB. Cytokine pattern during asymptomatic Anaplasma spp. infections and effect of co-infections by malaria and helminths in schoolchildren of Franceville, southeastern Gabon. Parasit Vectors 2025; 18:118. [PMID: 40148890 PMCID: PMC11948865 DOI: 10.1186/s13071-025-06714-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Accepted: 02/04/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND Asymptomatic infections by Anaplasma spp. and the basis of the immune response during these infections have not yet been established. This study investigated the inflammatory cytokine responses during Anaplasma spp. infection in school children and the effect of co-infection with Plasmodium spp. and helminths. METHODS Blood and stool samples were taken from children aged 5 to 17 years. Parasitological diagnosis was carried out by RDT and microscopy, while microscopy and PCR were used to diagnose infection by Anaplasma spp. Plasma was used for cytokine assays using the ELISA technique. RESULTS A total of 219 children were included in the present study, of whom 205 were infected with Anaplasma spp. and 14 were uninfected. Levels of IL-6, IL-22 and TGF-β were lower not only in children mono-infected with Anaplasma spp. but also in those co-infected with Anaplasma spp. and Plasmodium spp., Anaplasma spp. and helminths, and Anaplasma spp., Plasmodium spp. and helminths compared to controls. However, higher levels of IL-6 and IL-22 were observed in children mono-infected with Anaplasma spp. compared to those co-infected with Anaplasma spp. and helminths. The latter group also had lower levels of IL-6, IL-22, TGF-β and IL-10 than children co-infected with Anaplasma spp. and Plasmodium spp. In addition, children co-infected with Anaplasma spp. and helminths had also lower TGF-β and IL-10 levels than children co-infected with Anaplasma spp., Plasmodium spp. and helminths. An increase of IFN-γ and IL-10 were observed in children co-infected with Anaplasma spp. and Plasmodium spp. compared to those mono-infected with Anaplasma spp. Finally, the results showed that febrile children infected with Anaplasma spp. had higher levels of IFN-γ and lower levels of TGF-β than afebrile children. CONCLUSIONS These results suggest that infection with Anaplasma spp. downregulates cytokines including IL-6, IL-22 and TGF-β and that co-infection with Plasmodium spp. might have a protective effect on the host, while co-infection with helminths might have a negative effect.
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Affiliation(s)
- Chérone Nancy Mbani Mpega Ntigui
- Unité d'Evolution Epidémiologie et Résistances Parasitaires (UNEEREP), Centre Interdisciplinaire de Recherches Médicales de Franceville (CIRMF), BP 769, Franceville, Gabon.
- Ecole Doctorale Régionale d'Afrique Centrale en Infectiologie Tropicale (ECODRAC), Université des Sciences et Techniques de Masuku, BP 876, Franceville, Gabon.
| | - Sandrine Lydie Oyegue-Liabagui
- Unité d'Evolution Epidémiologie et Résistances Parasitaires (UNEEREP), Centre Interdisciplinaire de Recherches Médicales de Franceville (CIRMF), BP 769, Franceville, Gabon
- Ecole Doctorale Régionale d'Afrique Centrale en Infectiologie Tropicale (ECODRAC), Université des Sciences et Techniques de Masuku, BP 876, Franceville, Gabon
- Département de Biologie, Université des Sciences et Techniques de Masuku (USTM), BP 914, Franceville, Gabon
| | - Jenny Mouloungui-Mavoungou
- Unité d'Evolution Epidémiologie et Résistances Parasitaires (UNEEREP), Centre Interdisciplinaire de Recherches Médicales de Franceville (CIRMF), BP 769, Franceville, Gabon
| | - Nal Kennedy Ndjangangoye
- Unité d'Evolution Epidémiologie et Résistances Parasitaires (UNEEREP), Centre Interdisciplinaire de Recherches Médicales de Franceville (CIRMF), BP 769, Franceville, Gabon
| | - Desly Luide Madoungou Idoumi
- Unité d'Evolution Epidémiologie et Résistances Parasitaires (UNEEREP), Centre Interdisciplinaire de Recherches Médicales de Franceville (CIRMF), BP 769, Franceville, Gabon
| | - Lady Charlene Kouna
- Unité d'Evolution Epidémiologie et Résistances Parasitaires (UNEEREP), Centre Interdisciplinaire de Recherches Médicales de Franceville (CIRMF), BP 769, Franceville, Gabon
| | - Roland Fabrice Kassa Kassa
- Unité de Recherches d'Analyses Médicales (URAM), Centre Interdisciplinaire de Recherches Médicales de Franceville (CIRMF), BP 769, Franceville, Gabon
| | - Nancy Diamella Moukodoum
- Unité d'Evolution Epidémiologie et Résistances Parasitaires (UNEEREP), Centre Interdisciplinaire de Recherches Médicales de Franceville (CIRMF), BP 769, Franceville, Gabon
| | - Steede Seinnat Ontoua
- Unité d'Evolution Epidémiologie et Résistances Parasitaires (UNEEREP), Centre Interdisciplinaire de Recherches Médicales de Franceville (CIRMF), BP 769, Franceville, Gabon
| | - Roméo Karl Imboumy Limoukou
- Unité d'Evolution Epidémiologie et Résistances Parasitaires (UNEEREP), Centre Interdisciplinaire de Recherches Médicales de Franceville (CIRMF), BP 769, Franceville, Gabon
| | - Jean-Claude Biteghe Bi Essone
- Unité d'Evolution Epidémiologie et Résistances Parasitaires (UNEEREP), Centre Interdisciplinaire de Recherches Médicales de Franceville (CIRMF), BP 769, Franceville, Gabon
| | - Alain Prince Okouga
- Unité d'Evolution Epidémiologie et Résistances Parasitaires (UNEEREP), Centre Interdisciplinaire de Recherches Médicales de Franceville (CIRMF), BP 769, Franceville, Gabon
| | - Félicien Bagueboussa
- Unité d'Evolution Epidémiologie et Résistances Parasitaires (UNEEREP), Centre Interdisciplinaire de Recherches Médicales de Franceville (CIRMF), BP 769, Franceville, Gabon
| | - Jean-Bernard Lekana-Douki
- Unité d'Evolution Epidémiologie et Résistances Parasitaires (UNEEREP), Centre Interdisciplinaire de Recherches Médicales de Franceville (CIRMF), BP 769, Franceville, Gabon
- Département de Parasitologie-Mycologie, Université des Sciences de la Santé (USS), BP 4009, Libreville, Gabon
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Mair I, Fenn J, Wolfenden A, Lowe AE, Bennett A, Muir A, Thompson J, Dieumerci O, Logunova L, Shultz S, Bradley JE, Else KJ. The adaptive immune response to Trichuris in wild versus laboratory mice: An established model system in context. PLoS Pathog 2024; 20:e1012119. [PMID: 38626206 PMCID: PMC11051619 DOI: 10.1371/journal.ppat.1012119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 04/26/2024] [Accepted: 03/13/2024] [Indexed: 04/18/2024] Open
Abstract
Laboratory model organisms have provided a window into how the immune system functions. An increasing body of evidence, however, suggests that the immune responses of naive laboratory animals may differ substantially to those of their wild counterparts. Past exposure, environmental challenges and physiological condition may all impact on immune responsiveness. Chronic infections of soil-transmitted helminths, which we define as establishment of adult, fecund worms, impose significant health burdens on humans, livestock and wildlife, with limited treatment success. In laboratory mice, Th1 versus Th2 immune polarisation is the major determinant of helminth infection outcome. Here we compared antigen-specific immune responses to the soil-transmitted whipworm Trichuris muris between controlled laboratory and wild free-ranging populations of house mice (Mus musculus domesticus). Wild mice harbouring chronic, low-level infections produced lower levels of cytokines in response to Trichuris antigen than laboratory-housed C57BL/6 mice. Wild mouse effector/memory CD4+ T cell phenotype reflected the antigen-specific cytokine response across the Th1/Th2 spectrum. Increasing egg shedding was associated with body condition loss. However, local Trichuris-specific Th1/Th2 balance was positively associated with worm burden only in older wild mice. Thus, although the fundamental relationships between the CD4+ T helper cell response and resistance to T. muris infection are similar in both laboratory and wild M. m. domesticus, there are quantitative differences and age-specific effects that are analogous to human immune responses. These context-dependent immune responses demonstrate the fundamental importance of understanding the differences between model and natural systems for translating mechanistic models to 'real world' immune function.
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Affiliation(s)
- Iris Mair
- Lydia Becker Institute of Immunology and Inflammation, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
- Manchester Environmental Research Institute, Department of Earth and Environmental Sciences, Faculty of Science and Engineering, University of Manchester, Manchester, United Kingdom
| | - Jonathan Fenn
- School of Life Sciences, University of Nottingham, Nottingham, United Kingdom
| | - Andrew Wolfenden
- School of Life Sciences, University of Nottingham, Nottingham, United Kingdom
| | - Ann E. Lowe
- School of Life Sciences, University of Nottingham, Nottingham, United Kingdom
| | - Alex Bennett
- Lydia Becker Institute of Immunology and Inflammation, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
| | - Andrew Muir
- Lydia Becker Institute of Immunology and Inflammation, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
| | - Jacob Thompson
- Lydia Becker Institute of Immunology and Inflammation, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
| | - Olive Dieumerci
- Lydia Becker Institute of Immunology and Inflammation, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
| | - Larisa Logunova
- Lydia Becker Institute of Immunology and Inflammation, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
| | - Susanne Shultz
- School of Natural Sciences, Faculty of Science and Engineering, University of Manchester, Manchester, United Kingdom
| | - Janette E. Bradley
- School of Life Sciences, University of Nottingham, Nottingham, United Kingdom
| | - Kathryn J. Else
- Lydia Becker Institute of Immunology and Inflammation, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
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Adjobimey T, Meyer J, Hennenfent A, Bara AJ, Lagnika L, Kocou B, Adjagba M, Laleye A, Hoerauf A, Parcina M. Negative association between ascaris lumbricoides seropositivity and Covid-19 severity: insights from a study in Benin. Front Immunol 2023; 14:1233082. [PMID: 37622109 PMCID: PMC10446766 DOI: 10.3389/fimmu.2023.1233082] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Accepted: 07/20/2023] [Indexed: 08/26/2023] Open
Abstract
Introduction The COVID-19 pandemic has had devastating effects worldwide, but the trajectory of the pandemic has been milder in Low-and-Middle-Income Countries (LMICs), including those in Africa. Co-infection with helminths, such as Ascaris lumbricoides, has been suggested as a possible factor contributing to the reduced severity observed in these regions. Methods The present study investigated the association between Ascaris-specific antibody levels and COVID-19 severity in 276 SARS-CoV-2-infected individuals in Benin. Participants were categorized into asymptomatic (n=100), mild (n=150), and severe (n=26) groups based on clinical disease severity. Sera were collected and analyzed using ELISA to measure Ascaris and SARS-CoV-2-specific antibodies, while Luminex was used to assess cytokines and SARS-CoV-2-specific neutralizing antibody expression. Results and discussion The results demonstrated that asymptomatic SARS-CoV-2 seropositive individuals expressed, on average, 1.7 and 2.2-times higher levels of Ascaris antibodies compared to individuals with mild and severe COVID-19, respectively. This finding suggests an inverse correlation between Ascaris antibody levels and COVID-19 severity. Notably, logistic regression analysis showed that Ascaris seropositivity was significantly associated with a reduced risk of severe COVID-19 (OR = 0.277, p = 0.021). Interestingly, COVID-19 patients with comorbidities such as type 2 diabetes and high blood pressure showed lower expression of Ascaris antibodies. Strikingly, no correlation was observed between Ascaris antibody levels and SARS-CoV-2-specific neutralizing antibodies. On the other hand, individuals seronegative for Ascaris displayed significantly higher levels of systemic pro-inflammatory markers compared to seropositive individuals. These findings suggest that higher expression of Ascaris antibodies is associated with asymptomatic SARS-CoV-2 infections and may contribute to the reduction of the risk to develop severe COVID-19. The beneficial effect of Ascaris seropositivity on COVID-19 outcomes in Benin may be attributed to a decrease in comorbidities and pro-inflammatory markers. These observations provide valuable insights into the milder COVID-19 trajectory observed in Africa and may have implications for future therapeutic strategies.
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Affiliation(s)
- Tomabu Adjobimey
- Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany
- Laboratoire de Biologie intégrative pour l’Innovation thérapeutique (BioInov), Faculté des Sciences et Techniques (FAST), Université d’Abomey Calavi, Abomey Calavi, Benin
| | - Julia Meyer
- Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany
| | - Anneka Hennenfent
- Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany
| | - Anick J. Bara
- Laboratoire de Biologie intégrative pour l’Innovation thérapeutique (BioInov), Faculté des Sciences et Techniques (FAST), Université d’Abomey Calavi, Abomey Calavi, Benin
| | - Latifou Lagnika
- Laboratoire de Biologie intégrative pour l’Innovation thérapeutique (BioInov), Faculté des Sciences et Techniques (FAST), Université d’Abomey Calavi, Abomey Calavi, Benin
| | - Bienvenu Kocou
- Laboratoire de Biologie intégrative pour l’Innovation thérapeutique (BioInov), Faculté des Sciences et Techniques (FAST), Université d’Abomey Calavi, Abomey Calavi, Benin
| | - Marius Adjagba
- Laboratoire de Cytogénétique, Faculté des Sciences de la Santé (FSS), Université d’Abomey-Calavi, Cotonou, Benin
| | - Anatole Laleye
- Laboratoire de Cytogénétique, Faculté des Sciences de la Santé (FSS), Université d’Abomey-Calavi, Cotonou, Benin
| | - Achim Hoerauf
- Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany
- Bonn-Cologne Site, German Center for Infectious Disease Research (DZIF), Bonn, Germany
| | - Marijo Parcina
- Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany
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Lebu S, Kibone W, Muoghalu CC, Ochaya S, Salzberg A, Bongomin F, Manga M. Soil-transmitted helminths: A critical review of the impact of co-infections and implications for control and elimination. PLoS Negl Trop Dis 2023; 17:e0011496. [PMID: 37561673 PMCID: PMC10414660 DOI: 10.1371/journal.pntd.0011496] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/12/2023] Open
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.
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Affiliation(s)
- Sarah Lebu
- The Water Institute at UNC, Department of Environmental Sciences and Engineering, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
| | - Winnie Kibone
- School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Chimdi C. Muoghalu
- The Water Institute at UNC, Department of Environmental Sciences and Engineering, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
| | - Stephen Ochaya
- Department of Microbiology and Immunology, Faculty of Medicine, Gulu University, Gulu, Uganda
- Department of Biology, Faculty of Science, Gulu University, Gulu, Uganda
- Department of Clinical Pathology, Uppsala Academic Hospital, Uppsala, Sweden
| | - Aaron Salzberg
- The Water Institute at UNC, Department of Environmental Sciences and Engineering, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
| | - Felix Bongomin
- Department of Microbiology and Immunology, Faculty of Medicine, Gulu University, Gulu, Uganda
| | - Musa Manga
- The Water Institute at UNC, Department of Environmental Sciences and Engineering, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
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Tan PY, Loganathan R, Teng KT, Lee SC, Syahirah Nadiah Mohd J, Selvaduray KR, Ngui R, Lim YAL. Red palm olein-enriched biscuit supplementation lowers Ascaris lumbricoides reinfection at 6-month after anthelmintic treatment among schoolchildren with vitamin A deficiency (VAD). Acta Trop 2023; 240:106860. [PMID: 36775004 PMCID: PMC10241531 DOI: 10.1016/j.actatropica.2023.106860] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 01/10/2023] [Accepted: 02/08/2023] [Indexed: 02/12/2023]
Abstract
Notwithstanding the global efforts made to control intestinal parasitic infections, soil-transmitted helminth (STH) infections are still one of the most prevalent infections globally, especially in developing countries. A double-blinded, randomized controlled trial was conducted on 343 primary schoolchildren (8-12 years old) with vitamin A deficiency (VAD) in rural areas of Malaysia to investigate the effects of red palm olein (RPO)-enriched biscuits on STH reinfection rates and infection intensities. The effects of the RPO-enriched biscuits (experimental group, n = 153) and palm olein (PO)-enriched biscuits (control group, n = 190), were assessed at 3- and 6-month after the administration of complete triple-dose albendazole (one dose of 400 mg for three consecutive days). The overall STH infection rate at baseline was recorded at 65.6%. At 6-month, a significantly lower reinfection rate of A. lumbricoides was observed in the experimental group (35.3%) compared to the control group (60.0%) (P< 0.05), and a significant reduction in fecal egg count (epg) of A. lumbricoides was observed in the experimental group from baseline (P< 0.001), but no significant reduction was observed in the control group. No significant differences in the reduction of infection intensities of T. trichiura and hookworm were observed between experimental and control groups at 3- and 6-month (P>0.05). These findings suggest the potential beneficial effects of RPO-enriched biscuit supplementation on the reinfection of A. lumbricoides, which could be attributed to its high carotenoids content by enhancing host immune response and mucosal epithelium integrity. However, further studies are warranted to confirm whether RPO supplementation could result in similar parasite-specific beneficial effects in other community settings, as well as to explore the underlying mechanisms.
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Affiliation(s)
- Pei Yee Tan
- Nutrition Unit, Division of Product Development and Advisory Services, Malaysian Palm Oil Board, No. 6, Persiaran Institusi, Bandar Baru Bangi, 43000, Kajang, Selangor, Malaysia
- Department of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia
| | - Radhika Loganathan
- Nutrition Unit, Division of Product Development and Advisory Services, Malaysian Palm Oil Board, No. 6, Persiaran Institusi, Bandar Baru Bangi, 43000, Kajang, Selangor, Malaysia
| | - Kim-Tiu Teng
- Nutrition Unit, Division of Product Development and Advisory Services, Malaysian Palm Oil Board, No. 6, Persiaran Institusi, Bandar Baru Bangi, 43000, Kajang, Selangor, Malaysia
| | - Soo Ching Lee
- Type 2 Immunity Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD, United States
| | | | - Kanga Rani Selvaduray
- Nutrition Unit, Division of Product Development and Advisory Services, Malaysian Palm Oil Board, No. 6, Persiaran Institusi, Bandar Baru Bangi, 43000, Kajang, Selangor, Malaysia
| | - Romano Ngui
- Department of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia
| | - Yvonne Ai-Lian Lim
- Department of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia
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In silico design of a polypeptide as a vaccine candidate against ascariasis. Sci Rep 2023; 13:3504. [PMID: 36864139 PMCID: PMC9981566 DOI: 10.1038/s41598-023-30445-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Accepted: 02/23/2023] [Indexed: 03/04/2023] Open
Abstract
Ascariasis is the most prevalent zoonotic helminthic disease worldwide, and is responsible for nutritional deficiencies, particularly hindering the physical and neurological development of children. The appearance of anthelmintic resistance in Ascaris is a risk for the target of eliminating ascariasis as a public health problem by 2030 set by the World Health Organisation. The development of a vaccine could be key to achieving this target. Here we have applied an in silico approach to design a multi-epitope polypeptide that contains T-cell and B-cell epitopes of reported novel potential vaccination targets, alongside epitopes from established vaccination candidates. An artificial toll-like receptor-4 (TLR4) adjuvant (RS09) was added to improve immunogenicity. The constructed peptide was found to be non-allergic, non-toxic, with adequate antigenic and physicochemical characteristics, such as solubility and potential expression in Escherichia coli. A tertiary structure of the polypeptide was used to predict the presence of discontinuous B-cell epitopes and to confirm the molecular binding stability with TLR2 and TLR4 molecules. Immune simulations predicted an increase in B-cell and T-cell immune response after injection. This polypeptide can now be validated experimentally and compared to other vaccine candidates to assess its possible impact in human health.
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Bakery HH, Allam GA, Abuelsaad ASA, Abdel‐Latif M, Elkenawy AE, Khalil RG. Anti‐inflammatory, antioxidant, anti‐fibrotic, and schistosomicidal properties of plumbagin in murine schistosomiasis. Parasite Immunol 2022; 44:e12945. [DOI: 10.1111/pim.12945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 08/01/2022] [Accepted: 08/08/2022] [Indexed: 11/29/2022]
Affiliation(s)
- Heba H. Bakery
- Immunology Divisions, Zoology Department Faculty of Science, Beni‐Suef University Beni‐Suef Egypt
| | - Gamal A. Allam
- Immunology Divisions, Zoology Department Faculty of Science, Beni‐Suef University Beni‐Suef Egypt
| | | | - Mahmoud Abdel‐Latif
- Immunology Divisions, Zoology Department Faculty of Science, Beni‐Suef University Beni‐Suef Egypt
| | - Ayman E. Elkenawy
- Department of Pathology College of Medicine, Taif University, P.O. Box 11099 Taif Saudi Arabia
- Department of Molecular Biology, GEBRI University of Sadat City Sadat City Egypt
| | - Rehab G. Khalil
- Immunology Divisions, Zoology Department Faculty of Science, Beni‐Suef University Beni‐Suef Egypt
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Loke P, Lee SC, Oyesola OO. Effects of helminths on the human immune response and the microbiome. Mucosal Immunol 2022; 15:1224-1233. [PMID: 35732819 DOI: 10.1038/s41385-022-00532-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 05/17/2022] [Accepted: 05/22/2022] [Indexed: 02/04/2023]
Abstract
Helminths have evolved sophisticated immune regulating mechanisms to prevent rejection by their mammalian host. Our understanding of how the human immune system responds to these parasites remains poor compared to mouse models of infection and this limits our ability to develop vaccines as well as harness their unique properties as therapeutic strategies against inflammatory disorders. Here, we review how recent studies on human challenge infections, self-infected individuals, travelers, and endemic populations have improved our understanding of human type 2 immunity and its effects on the microbiome. The heterogeneity of responses between individuals and the limited access to tissue samples beyond the peripheral blood are challenges that limit human studies on helminths, but also provide opportunities to transform our understanding of human immunology. Organoids and single-cell sequencing are exciting new tools for immunological analysis that may aid this pursuit. Learning about the genetic and immunological basis of resistance, tolerance, and pathogenesis to helminth infections may thus uncover mechanisms that can be utilized for therapeutic purposes.
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Affiliation(s)
- P'ng Loke
- Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
| | - Soo Ching Lee
- Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA
| | - Oyebola O Oyesola
- Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA
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Rabiu OR, Dada-Adegbola H, Falade CO, Arinola OG, Odaibo AB, Ademowo OG. Serum cytokine profile of pregnant women with malaria, intestinal helminths and HIV infections in Ibadan, Nigeria. Parasitol Res 2022; 121:1983-1992. [PMID: 35522326 DOI: 10.1007/s00436-022-07531-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 04/25/2022] [Indexed: 11/25/2022]
Abstract
Malaria, helminthiasis and HIV are widespread in developing countries taking a heavy toll on pregnant women. Due to similar environmental and human factors of transmission, they co-exist. The epidemiology and pathology of these diseases have been extensively studied but data on serum cytokine profile changes which is crucial in pregnancy is limited. The aim of this study was to evaluate the co-infections and their impact on peripheral blood cytokines. Blood and stool samples were collected from recruited 18-45-year-old pregnant women in different trimesters who were apparently healthy with no obvious complications in pregnancy. Pretested questionnaires were administered for personal and socio-demographic details. Malaria parasitemia in Giemsa-stained thick blood films was examined microscopically. Stool samples were screened for helminths using Kato-Katz method. Cytokine levels of TNF-α, IFN-γ, IL-1α, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-13 and IL-17 in 121 serum samples were determined using ELISA. Data were analysed using descriptive statistics and Mann-Whitney U test at α0.05. Relative to the single infections, there were significant reductions in IFN-γ and IL-13 in second and third trimesters respectively in those with Plasmodium and helminth co-infection. IFN-γ and IL-17 were elevated while IL-1α and IL-12p70 were reduced in co-infection of helminths and HIV. Co-infection of Plasmodium and HIV in second and third trimesters showed significant elevations in IL-1α, IL-10 and IL-17 while TNF-α, IL-4 and IL-12p70 were significantly reduced. HIV in pregnancy and its co-infection with Plasmodium resulted in significant distortions in the cytokine profile. However, helminth and its co-infection with Plasmodium or HIV produced less changes in the cytokine profile.
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Affiliation(s)
- Olawunmi R Rabiu
- Department of Zoology, University of Ibadan, Ibadan, Nigeria
- Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria
- Department of Biological Sciences, Mountain Top University, Prayer City, Ogun State, Nigeria
| | - Hannah Dada-Adegbola
- Department of Medical Microbiology and Parasitology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Catherine O Falade
- Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria
- Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan, Nigeria
| | - Olatunbosun G Arinola
- Department of Immunology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | | | - Olusegun G Ademowo
- Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria.
- Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan, Nigeria.
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10
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Shlash SA, Alzubaidi ZF, Saleh HA. Cytokine production in Ancylostoma duodenale infection. J Med Life 2022; 15:479-482. [PMID: 35646178 PMCID: PMC9126450 DOI: 10.25122/jml-2021-0383] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 02/14/2022] [Indexed: 11/14/2022] Open
Abstract
Cytokine response to Ancylostoma duodenale (A. duodenale) infection was measured after starting treatments with piperazine. This study aims to determine the impact of cytokine production after infection with A. duodenale before and after treatment with piperazine. Blood and stool samples of 50 patients with A. duodenale infection and 28 healthy individuals (control) were collected. In this study, IFNγ, IL-5, IL-12, and IL-13 in serum (using ELISA-based methods) were measured. Stool samples were examined using the Kato-Katz technique to detect A. duodenale parasites. Blood and stool samples were analyzed 14 days after starting piperazine treatment for A. duodenale infection. The medium concentration of IFNγ, IL-5, IL-12, and IL-13 in the serum samples with A. duodenale infection is higher than that of the control group. IFNγ, IL-5, IL-12, and IL-13 levels were significantly higher in the infected individuals (10.5±7.4 pg/ml, 14.6±5.1 pg/ml, 8.5±3.2 pg/ml and 13.6±7.5 pg/ml respectively) than the control group (4.7±2.4 pg/ml, 7.8±4.06 pg/ml, 6.3±3.4 pg/ml and 3.5±2.7 pg/ml respectively). Also, piperazine treatment can significantly reduce cytokines levels (IFN-γ: P=0.043, IL-5: P=0.02, and IL-12, p=0.001). This study shows that piperazine treatment can reduce cytokines profiles in patients with A. duodenale infection.
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Affiliation(s)
| | - Zubaida Falih Alzubaidi
- Department of Clinical Laboratory Sciences, Faculty of Pharmacy, University of Kufa, Kufa, Iraq,Corresponding Author: Zubaida Falih Alzubaidi, Department of Clinical Laboratory Sciences, Faculty of Pharmacy, University of Kufa, Kufa, Iraq. E-mail:
| | - Huda Ali Saleh
- Department of Clinical Laboratory Sciences, Faculty of Pharmacy, University of Kufa, Kufa, Iraq
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11
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Corripio-Miyar Y, Hayward A, Lemon H, Sweeny AR, Bal X, Kenyon F, Pilkington JG, Pemberton JM, Nussey DH, McNeilly TN. Functionally distinct T-helper cell phenotypes predict resistance to different types of parasites in a wild mammal. Sci Rep 2022; 12:3197. [PMID: 35210503 PMCID: PMC8873199 DOI: 10.1038/s41598-022-07149-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 02/04/2022] [Indexed: 12/31/2022] Open
Abstract
The adaptive immune system is critical to an effective response to infection in vertebrates, with T-helper (Th) cells pivotal in orchestrating these responses. In natural populations where co-infections are the norm, different Th responses are likely to play an important role in maintaining host health and fitness, a relationship which remains poorly understood in wild animals. In this study, we characterised variation in functionally distinct Th responses in a wild population of Soay sheep by enumerating cells expressing Th-subset specific transcription factors and quantifying Th-associated cytokines. We tested the prediction that raised Th1 and Th2 responses should predict reduced apicomplexan and helminth parasite burdens, respectively. All measures of Th-associated cytokine production increased with age, while Th17- and regulatory Th-associated cytokine production increased more rapidly with age in males than females. Independent of age, sex, and each other, IL-4 and Gata3 negatively predicted gastro-intestinal nematode faecal egg count, while IFN-γ negatively predicted coccidian faecal oocyst count. Our results provide important support from outside the laboratory that Th1 and Th2 responses predict resistance to different kinds of parasites, and illustrate how harnessing specific reagents and tools from laboratory immunology will illuminate our understanding of host-parasite interactions in the wild.
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Affiliation(s)
- Yolanda Corripio-Miyar
- Moredun Research Institute, Pentlands Science Park, Bush Loan, Midlothian, EH26 0PZ, UK.
| | - Adam Hayward
- Moredun Research Institute, Pentlands Science Park, Bush Loan, Midlothian, EH26 0PZ, UK
| | - Hannah Lemon
- Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3FL, UK
| | - Amy R Sweeny
- Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3FL, UK
| | - Xavier Bal
- Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3FL, UK
| | - Fiona Kenyon
- Moredun Research Institute, Pentlands Science Park, Bush Loan, Midlothian, EH26 0PZ, UK
| | - Jill G Pilkington
- Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3FL, UK
| | - Josephine M Pemberton
- Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3FL, UK
| | - Daniel H Nussey
- Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3FL, UK
| | - Tom N McNeilly
- Moredun Research Institute, Pentlands Science Park, Bush Loan, Midlothian, EH26 0PZ, UK
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12
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Dana D, Roose S, Vlaminck J, Ayana M, Mekonnen Z, Geldhof P, Levecke B. Longitudinal assessment of the exposure to Ascaris lumbricoides through copromicroscopy and serology in school children from Jimma Town, Ethiopia. PLoS Negl Trop Dis 2022; 16:e0010131. [PMID: 35041666 PMCID: PMC8797258 DOI: 10.1371/journal.pntd.0010131] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 01/28/2022] [Accepted: 01/02/2022] [Indexed: 11/24/2022] Open
Abstract
Background We previously demonstrated that serology holds promise as an alternative diagnostic tool to copromicroscopy to monitor and evaluate deworming programs targeting soil-transmitted helminths (STHs). Here we explored the dynamics of anti-Ascaris antibodies (Ab) and evaluated the Ab-isotype of choice to assess the longitudinal exposure to Ascaris in Ethiopian school children. Methodology Between October 2018 and February 2020, stool and blood samples were collected every four months from school children (4 to 6 years of age). Stool samples were analyzed by duplicate Kato-Katz to assess the presence and intensity of any STH infection. Plasma Ab-responses against the total extract of Ascaris suum lung third stage larvae were measured through in-house Ab-ELISA’s for seven different Ab-isotypes. Principal findings At baseline, 42.4% of the 66 children were excreting eggs of any STH, Trichuris (37.9%) being the most prevalent. The cumulative prevalence (proportion of children tested that positive at least once over the entire study period) was 56.1% for Trichuris and 31.8% for Ascaris. For Ascaris, re-infections were frequently observed, whereas for Trichuris, children often remained excreting eggs following drug administration. When measuring anti-Ascaris Ab-levels, the cumulative seroprevalence was generally higher (IgG4: 60.6%; IgG1: 50.0%; IgE: 36.4%). The individual anti-Ascaris IgG4 levels at baseline were positively associated with the fecal egg counts averaged over the study period, the rate of egg-appearance and the number of positive test results. There was no apparent cross-reactivity between the anti-Ascaris IgG4 Ab-ELISA and Trichuris. Conclusions/Significance We demonstrate that the children are exposed to STH before the age of four and that the exposure to Ascaris is underestimated when measured with copromicroscopy. Compared to other Ab-isotypes, IgG4 is the Ab-isotype of choice to measure Ascaris exposure in STH endemic settings. Finally, the results also highlight that measuring anti-Ascaris IgG4 levels holds promise as a tool to identify individuals at higher risk for continued exposure to this STH. World-wide large-scale deworming programs are being implemented to control the morbidity attributable to intestinal worms. Our group has recently shown that diagnostic tools that detect anti-parasite antibodies hold promise as an alternative to the current diagnostic standard (detecting worm eggs in stool using microscopy) to monitor and evaluate the progress of these programs towards the set targets. In the present study, we further explored the potential of antibody-based assays by monitoring the exposure of Ethiopian school children during a 17-month period to worm infections. Our results indicated that children in this area are exposed to intestinal worms from an early age onwards and that, based on serological results, more children are exposed to worm infections than measured by the current diagnostic standard. In addition, we demonstrated that test results of the antibody assay at the start of the study were positively associated with mean egg counts averaged over the study period, the rate of egg-appearance and the number of positive stool tests, highlighting that such assay holds promise as a tool to identify individuals at higher high risk for continued exposure to worms, and ultimately improve control programs.
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Affiliation(s)
- Daniel Dana
- School of Laboratory Science, Faculty of Health Science, Institute of Health Jimma University, Jimma, Ethiopia
- Department of Translational Physiology, Infectiology and Public Health, Ghent University, Merelbeke, Belgium
- * E-mail: (DD); (BL)
| | - Sara Roose
- Department of Translational Physiology, Infectiology and Public Health, Ghent University, Merelbeke, Belgium
| | - Johnny Vlaminck
- Department of Translational Physiology, Infectiology and Public Health, Ghent University, Merelbeke, Belgium
| | - Mio Ayana
- School of Laboratory Science, Faculty of Health Science, Institute of Health Jimma University, Jimma, Ethiopia
- Department of Translational Physiology, Infectiology and Public Health, Ghent University, Merelbeke, Belgium
| | - Zeleke Mekonnen
- School of Laboratory Science, Faculty of Health Science, Institute of Health Jimma University, Jimma, Ethiopia
| | - Peter Geldhof
- Department of Translational Physiology, Infectiology and Public Health, Ghent University, Merelbeke, Belgium
| | - Bruno Levecke
- Department of Translational Physiology, Infectiology and Public Health, Ghent University, Merelbeke, Belgium
- * E-mail: (DD); (BL)
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13
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Age-dependent rise in IFN-γ competence undermines effective type 2 responses to nematode infection. Mucosal Immunol 2022; 15:1270-1282. [PMID: 35690651 PMCID: PMC9705248 DOI: 10.1038/s41385-022-00519-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 04/12/2022] [Accepted: 04/21/2022] [Indexed: 02/06/2023]
Abstract
The efficient induction of type 2 immune responses is central to the control of helminth infections. Previous studies demonstrated that strong Th1 responses driven by intracellular pathogens as well as a bias for type 1 activity in senescent mice impedes the generation of Th2 responses and the control of intestinal nematode infections. Here, we show that the spontaneous differentiation of Th1 cells and their expansion with age restrains type 2 immunity to infection with the small intestinal nematode H. polygyrus much earlier in life than previously anticipated. This includes the more extensive induction of IFN-γ competent, nematode-specific Th2/1 hybrid cells in BALB/c mice older than three months compared to younger animals. In C57BL/6 mice, Th1 cells accumulate more rapidly at steady state, translating to elevated Th2/1 differentiation and poor control of parasite fitness in primary infections experienced at a young age. Blocking of early IFN-γ and IL-12 signals during the first week of nematode infection leads to sharply decreased Th2/1 differentiation and promotes resistance in both mouse lines. Together, these data suggest that IFN-γ competent, type 1 like effector cells spontaneously accumulating in the vertebrate host progressively curtail the effectiveness of anti-nematode type 2 responses with rising host age.
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14
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The yin and yang of human soil-transmitted helminth infections. Int J Parasitol 2021; 51:1243-1253. [PMID: 34774540 PMCID: PMC9145206 DOI: 10.1016/j.ijpara.2021.11.001] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 11/01/2021] [Accepted: 11/02/2021] [Indexed: 12/22/2022]
Abstract
The major soil-transmitted helminths that infect humans are the roundworms, whipworms and hookworms. Soil-transmitted helminth infections rank among the most important neglected tropical diseases in terms of morbidity, and almost one billion people are still infected with at least one species. While anthelmintic drugs are available, they do not offer long term protection against reinfection, precipitating the need for vaccines that provide long-term immunologic defense. Vaccine discovery and development is in advanced clinical development for hookworm infection, with a bivalent human hookworm vaccine in clinical trials in Brazil and Africa, but is in its infancy for both roundworm (ascariasis) and whipworm (trichuriasis) infections. One of the greatest hurdles to developing soil-transmitted helminth vaccines is the potent immunoregulatory properties of these helminths, creating a barrier to the induction of meaningful long-term protective immunity. While challenging for vaccinologists, this phenomenon presents unique opportunities to develop an entirely new class of anti-inflammatory drugs that capitalise on these immunomodulatory strategies. Epidemiologic studies and clinical trials employing experimental soil-transmitted helminth challenge models, when coupled with findings from animal models, show that at least some soil-transmitted helminth-derived molecules can protect against the onset of autoimmune, allergic and metabolic disorders, and several natural products with the desired bioactivity have been isolated and tested in pre-clinical settings. The yin and yang of soil-transmitted helminth infections reflect both the urgency for effective vaccines and the potential for new immunoregulatory molecules from parasite products.
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Mbani Mpega Ntigui CN, Oyegue‐Liabagui SL, Kouna LC, Imboumy KR, Tsafack Tegomo NP, Okouga AP, Ontoua S, Lekana‐Douki J. Inflammatory cytokine responses in children with asymptomatic malaria infection living in rural, semi-urban and urban areas in south-eastern Gabon. Clin Exp Immunol 2021; 206:395-409. [PMID: 34363699 PMCID: PMC8561699 DOI: 10.1111/cei.13653] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 07/30/2021] [Accepted: 08/02/2021] [Indexed: 12/31/2022] Open
Abstract
Cytokines are soluble mediators of the immune response, and their evolution influences the disease outcome. Gaining knowledge on cytokines has become important, as they can constitute biomarkers allowing the diagnosis of malaria and preventing severe forms of the disease. Here, we investigated 10 cytokines and their circulating levels in asymptomatic Gabonese children with Plasmodium falciparum infection living in urban, semi-urban and rural areas. Blood samples were collected from 273 schoolchildren (153 uninfected and 120 infected) aged 6 to 192 months. Hematological parameters were determined and P. falciparum diagnosis was performed using a rapid diagnosis test, microscopy and nested polymerase chain reaction (PCR). Plasma pro- [interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-12p70, IL-17A and IL-22] and anti-inflammatory [IL-10, IL-4, IL-13 and transforming growth factor (TGF)-β] cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA) and compared between asymptomatic-infected and uninfected children. Results revealed that without distinction of area, IL-10 and IL-6 levels were higher in infected compared to uninfected children; however, the pro- and anti-inflammatory ratios (IL-6/IL-10 and TNF-α/IL-10) were similar. Furthermore, with area distinction significantly elevated levels of IL-10 in these asymptomatic children were always accompanied by either significantly low or high levels of a proinflammatory cytokine. Also, comparison between asymptomatic-infected children from the three areas showed significantly lower IL-17A, IL-22 and TGF-β levels in urban area compared to semi-urban and rural areas. These results suggest that asymptomatic malaria infections induce significantly high inflammatory cytokine levels without modifying the balanced between pro- and anti-inflammatory cytokines and underline the higher exposure to infections of children in rural areas.
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Affiliation(s)
- Chérone Nancy Mbani Mpega Ntigui
- Unité d’Evolution Epidémiologie et Résistances Parasitaires (UNEEREP)Centre Interdisciplinaire de Recherches Médicales de Franceville (CIRMF)FrancevilleGabon
- Ecole Doctorale Régionale d’Afrique Centrale en Infectiologie Tropicale (ECODRAC)Université des Sciences et Techniques de MasukuFrancevilleGabon
| | - Sandrine Lydie Oyegue‐Liabagui
- Unité d’Evolution Epidémiologie et Résistances Parasitaires (UNEEREP)Centre Interdisciplinaire de Recherches Médicales de Franceville (CIRMF)FrancevilleGabon
- Ecole Doctorale Régionale d’Afrique Centrale en Infectiologie Tropicale (ECODRAC)Université des Sciences et Techniques de MasukuFrancevilleGabon
| | - Lady Charlene Kouna
- Unité d’Evolution Epidémiologie et Résistances Parasitaires (UNEEREP)Centre Interdisciplinaire de Recherches Médicales de Franceville (CIRMF)FrancevilleGabon
| | - Karl Roméo Imboumy
- Unité d’Evolution Epidémiologie et Résistances Parasitaires (UNEEREP)Centre Interdisciplinaire de Recherches Médicales de Franceville (CIRMF)FrancevilleGabon
| | - Nathalie Pernelle Tsafack Tegomo
- Unité d’Evolution Epidémiologie et Résistances Parasitaires (UNEEREP)Centre Interdisciplinaire de Recherches Médicales de Franceville (CIRMF)FrancevilleGabon
| | - Alain Prince Okouga
- Unité d’Evolution Epidémiologie et Résistances Parasitaires (UNEEREP)Centre Interdisciplinaire de Recherches Médicales de Franceville (CIRMF)FrancevilleGabon
| | - Seinnat Ontoua
- Unité d’Evolution Epidémiologie et Résistances Parasitaires (UNEEREP)Centre Interdisciplinaire de Recherches Médicales de Franceville (CIRMF)FrancevilleGabon
| | - Jean‐Bernard Lekana‐Douki
- Unité d’Evolution Epidémiologie et Résistances Parasitaires (UNEEREP)Centre Interdisciplinaire de Recherches Médicales de Franceville (CIRMF)FrancevilleGabon
- Département de Parasitologie‐MycologieUniversité des Sciences de la Santé (USS)LibrevilleGabon
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Wudneh F, Gebeyehu Y, Anberbir S. Asymptomatic Malaria and Helminths Coinfection and Its Association with Anemia among Primary School Children in Gedeo Zone, Southern Ethiopia: A Cross-Sectional Study. J Trop Med 2021; 2021:7742960. [PMID: 34552634 PMCID: PMC8452447 DOI: 10.1155/2021/7742960] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Accepted: 08/07/2021] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Asymptomatic malaria and helminths coinfection occurs mainly in the tropics and subtropics where poverty and sanitary practice favor its high prevalence. In the tropics, where malaria is endemic, helminths also thrive resulting in coinfection. This study aimed to access the prevalence of asymptomatic malaria and helminths coinfection and its contribution for anemia in primary school children of Gedeo Zone, Southern Ethiopia. Methodology. This was a cross-sectional study conducted among 413 primary school children from February to April 2020. Finger-prick blood samples were used to determine asymptomatic malaria and hemoglobin concentrations. Stool samples were collected and processed through formalin-ether concentration techniques to detect the presence of intestinal helminths. Data were double entered into Epi Data version 3.1 software and exported to SPSS version 20 for analysis. Pearson's chi-square and correlation analysis were performed as part of the statistical analyses. RESULT A total of 413 primary school children aged 6 to 16 years (mean age ± SD: 10.7 ± 2.64years) were enrolled in the study. 159 (38.5%) of school children were infected with at least one of the parasitic diseases. The overall prevalence of asymptomatic malaria and intestinal helminths was 46 (11.1%) and 113 (27.3%) respectively. Asymptomatic malaria and helminths coinfection was 29 (7%). Total of 39.1% of asymptomatic malaria-infected school children were anemic, which is statistically significant (P < 0.05). 15.9% of helminths-infected school children were anemic, not statistically significant (P > 0.05). The prevalence of anemia was 12 (41.3%) among coinfected students, which is statistically significant (P < 0.005). CONCLUSION Asymptomatic malaria and helminths coinfection affects the health status of considerable number of primary school children in the study area. Therefore, simultaneous combat against the two parasitic infections is crucial to improve health of the school children.
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Affiliation(s)
- Feven Wudneh
- Department of Medical Laboratory, College of Medicine and Health Sciences, Dilla University, Dilla, Ethiopia
| | - Yabibal Gebeyehu
- School of Medicine, College of Medicine and Health Sciences, Dilla University, Dilla, Ethiopia
| | - Sara Anberbir
- Department of Medical Laboratory, College of Medicine and Health Sciences, Dilla University, Dilla, Ethiopia
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Ondari E, Calvino-Sanles E, First NJ, Gestal MC. Eosinophils and Bacteria, the Beginning of a Story. Int J Mol Sci 2021; 22:8004. [PMID: 34360770 PMCID: PMC8347986 DOI: 10.3390/ijms22158004] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 07/16/2021] [Accepted: 07/23/2021] [Indexed: 12/17/2022] Open
Abstract
Eosinophils are granulocytes primarily associated with TH2 responses to parasites or immune hyper-reactive states, such as asthma, allergies, or eosinophilic esophagitis. However, it does not make sense from an evolutionary standpoint to maintain a cell type that is only specific for parasitic infections and that otherwise is somehow harmful to the host. In recent years, there has been a shift in the perception of these cells. Eosinophils have recently been recognized as regulators of immune homeostasis and suppressors of over-reactive pro-inflammatory responses by secreting specific molecules that dampen the immune response. Their role during parasitic infections has been well investigated, and their versatility during immune responses to helminths includes antigen presentation as well as modulation of T cell responses. Although it is known that eosinophils can present antigens during viral infections, there are still many mechanistic aspects of the involvement of eosinophils during viral infections that remain to be elucidated. However, are eosinophils able to respond to bacterial infections? Recent literature indicates that Helicobacter pylori triggers TH2 responses mediated by eosinophils; this promotes anti-inflammatory responses that might be involved in the long-term persistent infection caused by this pathogen. Apparently and on the contrary, in the respiratory tract, eosinophils promote TH17 pro-inflammatory responses during Bordetella bronchiseptica infection, and they are, in fact, critical for early clearance of bacteria from the respiratory tract. However, eosinophils are also intertwined with microbiota, and up to now, it is not clear if microbiota regulates eosinophils or vice versa, or how this connection influences immune responses. In this review, we highlight the current knowledge of eosinophils as regulators of pro and anti-inflammatory responses in the context of both infection and naïve conditions. We propose questions and future directions that might open novel research avenues in the future.
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Affiliation(s)
| | | | | | - Monica C. Gestal
- LSU Health, Department of Microbiology and Immunology, Louisiana State University (LSU), Shreveport, LA 71103, USA; (E.O.); (E.C.-S.); (N.J.F.)
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Rapaka RR, Cross AS, McArthur MA. Using Adjuvants to Drive T Cell Responses for Next-Generation Infectious Disease Vaccines. Vaccines (Basel) 2021; 9:vaccines9080820. [PMID: 34451945 PMCID: PMC8402546 DOI: 10.3390/vaccines9080820] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 07/16/2021] [Accepted: 07/20/2021] [Indexed: 12/12/2022] Open
Abstract
Using adjuvants to drive features of T cell responses to vaccine antigens is an important technological challenge in the design of new and improved vaccines against infections. Properties such as T helper cell function, T cell memory, and CD8+ T cell cytotoxicity may play critical roles in optimal and long-lived immunity through vaccination. Directly manipulating specific immune activation or antigen delivery pathways with adjuvants may selectively augment desired T cell responses in vaccination and may improve the effectiveness and durability of vaccine responses in humans. In this review we outline recently studied adjuvants in their potential for antigen presenting cell and T cell programming during vaccination, with an emphasis on what has been observed in studies in humans as available.
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Eloi da Silva T, Barbosa FS, Magalhães LMD, Gazzinelli-Guimarães PH, Dos Santos AC, Nogueira DS, Resende NM, Amorim CC, Gazzinelli-Guimarães AC, Viana AG, Geiger SM, Bartholomeu DC, Fujiwara RT, Bueno LL. Unraveling Ascaris suum experimental infection in humans. Microbes Infect 2021; 23:104836. [PMID: 34020024 DOI: 10.1016/j.micinf.2021.104836] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 04/19/2021] [Accepted: 04/20/2021] [Indexed: 12/31/2022]
Abstract
Ascaris lumbricoides and A. suum are two closely related parasites that infect humans and pigs. The zoonotic potential of A. suum has been a matter of debate for decades. Here we sought to investigate the potential human infection by A. suum and its immunological alterations. We orally infected five healthy human subjects with eggs embraced by A. suum. The infection was monitored for symptoms and possible respiratory changes, by an interdisciplinary health team. Parasitological, hematological analyses, serum immunoglobulin, cytokine profiles, and gene expression were evaluated during the infection. Our results show that A. suum is able to infect and complete the cycle in humans causing A. lumbricoides similar symptoms, including, cough, headache, diarrhea, respiratory discomfort and chest x-ray alterations coinciding with larvae migration in the lungs. We also observed activation of the immune system with production of IgM and IgG and a Th2/Th17 response with downregulation of genes related to Th1 and apoptosis. PCA (Principal componts analysis) show that infection with A. suum leads to a change in the immune landscape of the human host. Our data reinforce the zoonotic capacity of A. suum and bring a new perspective on the understanding of the immune response against this parasite.
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Affiliation(s)
- Thaís Eloi da Silva
- Parasitology Department, Institute of Biological Science, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Fernando S Barbosa
- Parasitology Department, Institute of Biological Science, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Luisa M D Magalhães
- Parasitology Department, Institute of Biological Science, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Pedro H Gazzinelli-Guimarães
- Parasitology Department, Institute of Biological Science, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; National Institutes of Health, National Institute of Allergy and Infectious Disease, Bethesda, Maryland, USA
| | - Anderson C Dos Santos
- Parasitology Department, Institute of Biological Science, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Denise S Nogueira
- Parasitology Department, Institute of Biological Science, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Nathalia M Resende
- Parasitology Department, Institute of Biological Science, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Chiara C Amorim
- Parasitology Department, Institute of Biological Science, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Ana Clara Gazzinelli-Guimarães
- Parasitology Department, Institute of Biological Science, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Agostinho G Viana
- Parasitology Department, Institute of Biological Science, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Stefan M Geiger
- Parasitology Department, Institute of Biological Science, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Daniella C Bartholomeu
- Parasitology Department, Institute of Biological Science, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Ricardo T Fujiwara
- Parasitology Department, Institute of Biological Science, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Lilian L Bueno
- Parasitology Department, Institute of Biological Science, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
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20
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Zaini A, Good-Jacobson KL, Zaph C. Context-dependent roles of B cells during intestinal helminth infection. PLoS Negl Trop Dis 2021; 15:e0009340. [PMID: 33983946 PMCID: PMC8118336 DOI: 10.1371/journal.pntd.0009340] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
The current approaches to reduce the burden of chronic helminth infections in endemic areas are adequate sanitation and periodic administration of deworming drugs. Yet, resistance against some deworming drugs and reinfection can still rapidly occur even after treatment. A vaccine against helminths would be an effective solution at preventing reinfection. However, vaccines against helminth parasites have yet to be successfully developed. While T helper cells and innate lymphoid cells have been established as important components of the protective type 2 response, the roles of B cells and antibodies remain the most controversial. Here, we review the roles of B cells during intestinal helminth infection. We discuss the potential factors that contribute to the context-specific roles for B cells in protection against diverse intestinal helminth parasite species, using evidence from well-defined murine model systems. Understanding the precise roles of B cells during resistance and susceptibility to helminth infection may offer a new perspective of type 2 protective immunity.
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Affiliation(s)
- Aidil Zaini
- Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
- Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
| | - Kim L. Good-Jacobson
- Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
- Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
| | - Colby Zaph
- Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
- Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
- * E-mail:
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21
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Mair I, Else KJ, Forman R. Trichuris muris as a tool for holistic discovery research: from translational research to environmental bio-tagging. Parasitology 2021; 148:1-13. [PMID: 33952360 PMCID: PMC8660646 DOI: 10.1017/s003118202100069x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 04/16/2021] [Accepted: 04/19/2021] [Indexed: 12/11/2022]
Abstract
Trichuris spp. (whipworms) are intestinal nematode parasites which cause chronic infections associated with significant morbidities. Trichuris muris in a mouse is the most well studied of the whipworms and research on this species has been approached from a number of different disciplines. Research on T. muris in a laboratory mouse has provided vital insights into the host–parasite interaction through analyses of the immune responses to infection, identifying factors underpinning host susceptibility and resistance. Laboratory studies have also informed strategies for disease control through anthelmintics and vaccine research. On the contrary, research on naturally occurring infections with Trichuris spp. allows the analysis of the host–parasite co-evolutionary relationships and parasite genetic diversity. Furthermore, ecological studies utilizing Trichuris have aided our knowledge of the intricate relationships amongst parasite, host and environment. More recently, studies in wild and semi-wild settings have combined the strengths of the model organism of the house mouse with the complexities of context-dependent physiological responses to infection. This review celebrates the extraordinarily broad range of beneficiaries of whipworm research, from immunologists and parasitologists, through epidemiologists, ecologists and evolutionary biologists to the veterinary and medical communities.
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Affiliation(s)
- Iris Mair
- Faculty of Biology, Medicine and Health, Lydia Becker Institute of Immunology and Inflammation, Manchester Academic Health Science Centre, The University of Manchester, Oxford Road, ManchesterM13 9PT, UK
| | - Kathryn J. Else
- Faculty of Biology, Medicine and Health, Lydia Becker Institute of Immunology and Inflammation, Manchester Academic Health Science Centre, The University of Manchester, Oxford Road, ManchesterM13 9PT, UK
| | - Ruth Forman
- Faculty of Biology, Medicine and Health, Lydia Becker Institute of Immunology and Inflammation, Manchester Academic Health Science Centre, The University of Manchester, Oxford Road, ManchesterM13 9PT, UK
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22
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Montaño KJ, Cuéllar C, Sotillo J. Rodent Models for the Study of Soil-Transmitted Helminths: A Proteomics Approach. Front Cell Infect Microbiol 2021; 11:639573. [PMID: 33968800 PMCID: PMC8100317 DOI: 10.3389/fcimb.2021.639573] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Accepted: 03/29/2021] [Indexed: 12/30/2022] Open
Abstract
Soil-transmitted helminths (STH) affect hundreds of millions worldwide and are some of the most important neglected tropical diseases in terms of morbidity. Due to the difficulty in studying STH human infections, rodent models have become increasingly used, mainly because of their similarities in life cycle. Ascaris suum and Trichuris muris have been proven appropriate and low maintenance models for the study of ascariasis and trichuriasis. In the case of hookworms, despite most of the murine models do not fully reproduce the life cycle of Necator americanus, their proteomic similarity makes them highly suitable for the development of novel vaccine candidates and for the study of hookworm biological features. Furthermore, these models have been helpful in elucidating some basic aspects of our immune system, and are currently being used by numerous researchers to develop novel molecules with immunomodulatory proteins. Herein we review the similarities in the proteomic composition between Nippostrongylus brasiliensis, Heligmosomoides polygyrus bakeri and Trichuris muris and their respective human counterpart with a focus on the vaccine candidates and immunomodulatory proteins being currently studied.
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Affiliation(s)
- Karen J Montaño
- Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain
| | - Carmen Cuéllar
- Departamento de Microbiología y Parasitología, Facultad de Farmacia, Universidad Complutense, Madrid, Spain
| | - Javier Sotillo
- Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain
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23
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Abo-Aziza FAM, Zaki AKA, Alajaji AI, Al Barrak SM. Bone marrow mesenchymal stem cell co-adjuvant therapy with albendazole for managing Toxocara vitulorum-rat model. Vet World 2021; 14:347-363. [PMID: 33776300 PMCID: PMC7994112 DOI: 10.14202/vetworld.2021.347-363] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 12/28/2020] [Indexed: 11/29/2022] Open
Abstract
Background and Aim: Toxocara vitulorum is a bovine intestinal nematode. Immune pictures following infection are conflicting and stopping anthelmintic albendazole treatment recording reversed liver abnormalities. The purpose of this work was to evaluate the therapeutic potential of bone marrow mesenchymal stem cells (BMMSCs) therapy, subsequent to albendazole administration in rats infected with T. vitulorum. Materials and Methods: The ultrasonographic and histopathological examinations as well as serum liver enzymes activity and the kinetics of recovery were investigated. The correlation of cell-mediated and humoral immune pictures was assessed by assaying immunoglobulins, splenocytes viability, phagocytic index, and Th1/Th2 cytokines. Results: The cultured BMMSCs counting were 4.21×104 cells/cm2 with 96.03% viability. Flow-cytometric analysis indicated positive CD90 (82%), CD105 (79%) and negative CD34 (0.37%), CD45 (0.42%), attesting to the suitability of the isolated BMMSCs for use in therapy. Transplantation of BMMSCs after albendazole administration significantly reduced the release of liver enzymes (p<0.05) indicating liver cellularity improvement. The ultrasonographic, macroscopic, and histopathological findings confirmed the biochemical results. Significant elevation in the levels of tumor necrosis factor (TNF)-α and interferon (INF)-γ with a decline in interleukin (IL)-4 was observed in the untreated model (p<0.05). However, albendazole treatment followed by BMMSCs therapy significantly lowered the release of TNF-α and INF-γ, associated with significant production of IL-4 and IL-10 (p<0.05). Conclusion: The final results indicated that the liver functions, histopathological findings, and immune parameters were aggravated after experimental T. vitulorum infection. Albendazole treatment followed by BMMSCs therapy was found to assist in regeneration of injured hepatic tissue. Besides, it appeared to modulate host defensive immune responses against T. vitulorum antigens. This work could define more clearly the events that manipulate the host immune, histopathological, and biochemical responses to minimize obstacles in using stem cell therapy in animal toxocariosis.
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Affiliation(s)
- Faten A M Abo-Aziza
- Department of Parasitology and Animal Diseases, Veterinary Research Division, National Research Centre, Cairo, Egypt
| | - Abdel Kader A Zaki
- Department of Physiology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.,Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Ahmed I Alajaji
- Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Saleh M Al Barrak
- Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
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24
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Comorbidity of Geo-Helminthes among Malaria Outpatients of the Health Facilities in Ethiopia: Systematic Review and Meta-Analysis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18030862. [PMID: 33498343 PMCID: PMC7908091 DOI: 10.3390/ijerph18030862] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 01/07/2021] [Accepted: 01/10/2021] [Indexed: 01/15/2023]
Abstract
Background: Coinfection of malaria and intestinal helminths affects one third of the global population, largely among communities with severe poverty. The spread of these parasitic infections overlays in several epidemiological locations and the host shows different outcomes. This systematic review and meta-analysis determine the pooled prevalence of malaria and intestinal helminthiases coinfections among malaria suspected patients in Ethiopia. Methods: Primary studies published in English language were retrieved using appropriate search terms on Google Scholar, PubMed/MEDLINE, CINHAL, Scopus, and Embase. The Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) was used for critical appraisal of studies. A pooled statistical meta-analysis was conducted using STATA Version 14.0 software. The heterogeneity and publication bias were assessed using the I2 statistics and Egger’s test, respectively. Duval and Tweedie’s nonparametric trim and fill analysis using the random-effect analysis. The Random effects model was used to estimate the summary prevalence of comorbidity of malaria and soil transmitted helminthiases and the corresponding 95% confidence intervals (CI). The review protocol has registered in PROSPERO number CRD42019144803. Results: We identified ten studies (n = 6633 participants) in this study. The overall pooled result showed 13% of the ambulatory patients infected by malaria and intestinal helminths concurrently in Ethiopia. The pooled prevalence of Plasmodium falciparum and Plasmodium vivax, and mixed infections were 12, 30, and 6%, respectively. The most common intestinal helminth parasites detected were Hookworm, Ascaris lumbricoides, and Tirchuris trichiura. Conclusions: The comorbidity of malaria and intestinal helminths causes lower hemoglobin level leading to maternal anemia, preterm delivery, and still birth in pregnant women and lactating mother. School-aged children and neonates coinfected by plasmodium species and soil transmitted helminths develop cognitive impairment, protein energy malnutrition, low birth weight, small for gestational age, and gross motor delay. The Ministry of Health of Ethiopia and its international partners working on malaria elimination programs should give more emphasis to the effect of the interface of malaria and soil transmitted helminths, which calls for an integrated disease control and prevention.
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25
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Gordon CA, Shield JM, Bradbury RS, Muhi S, Page W, Judd JA, Lee R, Biggs BA, Ross K, Kurscheid J, Gray DJ, McManus DP. HTLV-I and Strongyloides in Australia: The worm lurking beneath. ADVANCES IN PARASITOLOGY 2021; 111:119-201. [PMID: 33482974 DOI: 10.1016/bs.apar.2020.11.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Strongyloidiasis and HTLV-I (human T-lymphotropic virus-1) are important infections that are endemic in many countries around the world with an estimated 370 million infected with Strongyloides stercoralis alone, and 5-10 million with HTVL-I. Co-infections with these pathogens are associated with significant morbidity and can be fatal. HTLV-I infects T-cells thus causing dysregulation of the immune system which has been linked to dissemination and hyperinfection of S. stercoralis leading to bacterial sepsis which can result in death. Both of these pathogens are endemic in Australia primarily in remote communities in Queensland, the Northern Territory, and Western Australia. Other cases in Australia have occurred in immigrants and refugees, returned travellers, and Australian Defence Force personnel. HTLV-I infection is lifelong with no known cure. Strongyloidiasis is a long-term chronic disease that can remain latent for decades, as shown by infections diagnosed in prisoners of war from World War II and the Vietnam War testing positive decades after they returned from these conflicts. This review aims to shed light on concomitant infections of HTLV-I with S. stercoralis primarily in Australia but in the global context as well.
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Affiliation(s)
- Catherine A Gordon
- Infectious Diseases Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
| | - Jennifer M Shield
- Department of Pharmacy and Biomedical Sciences, La Trobe University, Bendigo, VIC, Australia; Department of Medicine, The Peter Doherty Institute for Infection and Immunity, University of Melbourne and the Royal Melbourne Hospital, Melbourne, VIC, Australia
| | - Richard S Bradbury
- School of Health and Life Sciences, Federation University, Berwick, VIC, Australia
| | - Stephen Muhi
- Victorian Infectious Diseases Service, The Royal Melbourne Hospital, Parkville, VIC, Australia
| | - Wendy Page
- College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, QLD, Australia
| | - Jenni A Judd
- School of Health Medical and Applied Sciences, Central Queensland University, Bundaberg, QLD, Australia; Centre for Indigenous Health Equity Research, Central Queensland University, Bundaberg, QLD, Australia
| | - Rogan Lee
- Westmead Clinical School, The University of Sydney, Westmead, NSW, Australia
| | - Beverley-Ann Biggs
- Department of Medicine, The Peter Doherty Institute for Infection and Immunity, University of Melbourne and the Royal Melbourne Hospital, Melbourne, VIC, Australia; Victorian Infectious Diseases Service, The Royal Melbourne Hospital, Parkville, VIC, Australia
| | - Kirstin Ross
- College of Science and Engineering, Flinders University, Adelaide, South Australia, Australia
| | - Johanna Kurscheid
- Department of Global Health, Research School of Population Health, Australian National University, Acton, ACT, Australia
| | - Darren J Gray
- Department of Global Health, Research School of Population Health, Australian National University, Acton, ACT, Australia
| | - Donald P McManus
- Infectious Diseases Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
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26
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Uhegbu K, Uhegbu V, Eyong K, Ikobah J, Ekanem E. Helminthic infestation in children aged 6 to 59 months with diarrhea in Calabar. NIGERIAN JOURNAL OF MEDICINE 2021. [DOI: 10.4103/njm.njm_69_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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27
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Chetty A, Omondi MA, Butters C, Smith KA, Katawa G, Ritter M, Layland L, Horsnell W. Impact of Helminth Infections on Female Reproductive Health and Associated Diseases. Front Immunol 2020; 11:577516. [PMID: 33329545 PMCID: PMC7719634 DOI: 10.3389/fimmu.2020.577516] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 10/27/2020] [Indexed: 12/25/2022] Open
Abstract
A growing body of knowledge exists on the influence of helminth infections on allergies and unrelated infections in the lung and gastrointestinal (GI) mucosa. However, the bystander effects of helminth infections on the female genital mucosa and reproductive health is understudied but important considering the high prevalence of helminth exposure and sexually transmitted infections in low- and middle-income countries (LMICs). In this review, we explore current knowledge about the direct and systemic effects of helminth infections on unrelated diseases. We summarize host disease-controlling immunity of important sexually transmitted infections and introduce the limited knowledge of how helminths infections directly cause pathology to female reproductive tract (FRT), alter susceptibility to sexually transmitted infections and reproduction. We also review work by others on type 2 immunity in the FRT and hypothesize how these insights may guide future work to help understand how helminths alter FRT health.
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Affiliation(s)
- Alisha Chetty
- Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Cape Town, South Africa
| | - Millicent A Omondi
- Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Cape Town, South Africa
| | - Claire Butters
- Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Cape Town, South Africa
| | - Katherine Ann Smith
- Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Cape Town, South Africa.,School of Biosciences, Cardiff University, Cardiff, United Kingdom
| | - Gnatoulma Katawa
- Ecole Supérieure des Techniques Biologiques et Alimentaires, Université de Lomé, Lomé, Togo
| | - Manuel Ritter
- Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn (UKB), Bonn, Germany
| | - Laura Layland
- Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn (UKB), Bonn, Germany
| | - William Horsnell
- Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Cape Town, South Africa.,Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
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28
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Zawawi A, Else KJ. Soil-Transmitted Helminth Vaccines: Are We Getting Closer? Front Immunol 2020; 11:576748. [PMID: 33133094 PMCID: PMC7565266 DOI: 10.3389/fimmu.2020.576748] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 09/02/2020] [Indexed: 01/07/2023] Open
Abstract
Parasitic helminths infect over one-fourth of the human population resulting in significant morbidity, and in some cases, death in endemic countries. Despite mass drug administration (MDA) to school-aged children and other control measures, helminth infections are spreading into new areas. Thus, there is a strong rationale for developing anthelminthic vaccines as cost-effective, long-term immunological control strategies, which, unlike MDA, are not haunted by the threat of emerging drug-resistant helminths nor limited by reinfection risk. Advances in vaccinology, immunology, and immunomics include the development of new tools that improve the safety, immunogenicity, and efficacy of vaccines; and some of these tools have been used in the development of helminth vaccines. The development of anthelminthic vaccines is fraught with difficulty. Multiple lifecycle stages exist each presenting stage-specific antigens. Further, helminth parasites are notorious for their ability to dampen down and regulate host immunity. One of the first significant challenges in developing any vaccine is identifying suitable candidate protective antigens. This review explores our current knowledge in lead antigen identification and reports on recent pre-clinical and clinical trials in the context of the soil-transmitted helminths Trichuris, the hookworms and Ascaris. Ultimately, a multivalent anthelminthic vaccine could become an essential tool for achieving the medium-to long-term goal of controlling, or even eliminating helminth infections.
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Affiliation(s)
- Ayat Zawawi
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia,*Correspondence: Ayat Zawawi
| | - Kathryn J. Else
- Manchester Academic Health Science Centre, Faculty of Biology, Medicine, and Health, School of Biological Sciences, Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, United Kingdom,Kathryn J. Else
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29
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Midha A, Ebner F, Schlosser-Brandenburg J, Rausch S, Hartmann S. Trilateral Relationship: Ascaris, Microbiota, and Host Cells. Trends Parasitol 2020; 37:251-262. [PMID: 33008723 DOI: 10.1016/j.pt.2020.09.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 09/02/2020] [Accepted: 09/04/2020] [Indexed: 12/11/2022]
Abstract
Ascariasis is a globally spread intestinal nematode infection of humans and a considerable concern in pig husbandry. Ascaris accomplishes a complex body migration from the intestine via the liver and lung before returning to the intestine. Tissue migration and the habitat shared with a complex microbial community pose the question of how the nematode interacts with microbes and host cells from various tissues. This review addresses the current knowledge of the trilateral relationship between Ascaris, its microbial environment, and host cells, and discusses novel approaches targeting these interactions to combat this widespread infection of livestock and man.
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Affiliation(s)
- Ankur Midha
- Institute of Immunology, Freie Universität Berlin, Robert von Ostertag-Str. 7-13, D-14163 Berlin, Germany
| | - Friederike Ebner
- Institute of Immunology, Freie Universität Berlin, Robert von Ostertag-Str. 7-13, D-14163 Berlin, Germany
| | | | - Sebastian Rausch
- Institute of Immunology, Freie Universität Berlin, Robert von Ostertag-Str. 7-13, D-14163 Berlin, Germany
| | - Susanne Hartmann
- Institute of Immunology, Freie Universität Berlin, Robert von Ostertag-Str. 7-13, D-14163 Berlin, Germany.
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30
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Colombo SAP, Grencis RK. Immunity to Soil-Transmitted Helminths: Evidence From the Field and Laboratory Models. Front Immunol 2020; 11:1286. [PMID: 32655568 PMCID: PMC7324686 DOI: 10.3389/fimmu.2020.01286] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 05/21/2020] [Indexed: 12/13/2022] Open
Abstract
Infection with soil-transmitted helminths (STH) remains a major burden on global health and agriculture. Our understanding of the immunological mechanisms that govern whether an individual is resistant or susceptible to infection is derived primarily from model infections in rodents. Typically, experimental infections employ an artificially high, single bolus of parasites that leads to rapid expulsion of the primary infection and robust immunity to subsequent challenges. However, immunity in natura is generated slowly, and is only partially effective, with individuals in endemic areas retaining low-level infections throughout their lives. Therefore, there is a gap between traditional model STH systems and observations in the field. Here, we review the immune response to traditional model STH infections in the laboratory. We compare these data to studies of natural infection in humans and rodents in endemic areas, highlighting crucial differences between experimental and natural infection. We then detail the literature to date on the use of "trickle" infections to experimentally model the kinetics of natural infection.
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Affiliation(s)
- Stefano A. P. Colombo
- Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
| | - Richard K. Grencis
- Division of Infection, Immunity and Respiratory Medicine, Wellcome Trust Centre for Cell Matrix Research, Lydia Becker Institute for Immunology and Inflammation, The University of Manchester, Manchester, United Kingdom
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31
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Else KJ, Keiser J, Holland CV, Grencis RK, Sattelle DB, Fujiwara RT, Bueno LL, Asaolu SO, Sowemimo OA, Cooper PJ. Whipworm and roundworm infections. Nat Rev Dis Primers 2020; 6:44. [PMID: 32467581 DOI: 10.1038/s41572-020-0171-3] [Citation(s) in RCA: 141] [Impact Index Per Article: 28.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/01/2020] [Indexed: 12/26/2022]
Abstract
Trichuriasis and ascariasis are neglected tropical diseases caused by the gastrointestinal dwelling nematodes Trichuris trichiura (a whipworm) and Ascaris lumbricoides (a roundworm), respectively. Both parasites are staggeringly prevalent, particularly in tropical and subtropical areas, and are associated with substantial morbidity. Infection is initiated by ingestion of infective eggs, which hatch in the intestine. Thereafter, T. trichiura larvae moult within intestinal epithelial cells, with adult worms embedded in a partially intracellular niche in the large intestine, whereas A. lumbricoides larvae penetrate the gut mucosa and migrate through the liver and lungs before returning to the lumen of the small intestine, where adult worms dwell. Both species elicit type 2 anti-parasite immunity. Diagnosis is typically based on clinical presentation (gastrointestinal symptoms and inflammation) and the detection of eggs or parasite DNA in the faeces. Prevention and treatment strategies rely on periodic mass drug administration (generally with albendazole or mebendazole) to at-risk populations and improvements in water, sanitation and hygiene. The effectiveness of drug treatment is very high for A. lumbricoides infections, whereas cure rates for T. trichiura infections are low. Novel anthelminthic drugs are needed, together with vaccine development and tools for diagnosis and assessment of parasite control in the field.
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Affiliation(s)
- Kathryn J Else
- Lydia Becker Institute for Immunology and Inflammation, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
| | - Jennifer Keiser
- Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.,University of Basel, Basel, Switzerland
| | - Celia V Holland
- Department of Zoology, School of Natural Sciences, Trinity College Dublin, Dublin, Ireland
| | - Richard K Grencis
- Lydia Becker Institute for Immunology and Inflammation, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
| | - David B Sattelle
- Centre for Respiratory Biology, UCL Respiratory, Rayne Building, University College London, London, UK
| | - Ricardo T Fujiwara
- Department of Parasitology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Lilian L Bueno
- Department of Parasitology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Samuel O Asaolu
- Department of Zoology, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria
| | - Oluyomi A Sowemimo
- Department of Zoology, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria
| | - Philip J Cooper
- Institute of Infection and Immunity, St George's University of London, London, UK.,Facultad de Ciencias Medicas, de la Salud y la Vida, Universidad Internacional del Ecuador, Quito, Ecuador
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Coakley G, Volpe B, Bouchery T, Shah K, Butler A, Geldhof P, Hatherill M, Horsnell WGC, Esser-von Bieren J, Harris NL. Immune serum-activated human macrophages coordinate with eosinophils to immobilize Ascaris suum larvae. Parasite Immunol 2020; 42:e12728. [PMID: 32394439 DOI: 10.1111/pim.12728] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 03/30/2020] [Accepted: 03/31/2020] [Indexed: 12/19/2022]
Abstract
Helminth infection represents a major health problem causing approximately 5 million disability-adjusted life years worldwide. Concerns that repeated anti-helminthic treatment may lead to drug resistance render it important that vaccines are developed but will require increased understanding of the immune-mediated cellular and antibody responses to helminth infection. IL-4 or antibody-activated murine macrophages are known to immobilize parasitic nematode larvae, but few studies have addressed whether this is translatable to human macrophages. In the current study, we investigated the capacity of human macrophages to recognize and attack larval stages of Ascaris suum, a natural porcine parasite that is genetically similar to the human helminth Ascaris lumbricoides. Human macrophages were able to adhere to and trap A suum larvae in the presence of either human or pig serum containing Ascaris-specific antibodies and other factors. Gene expression analysis of serum-activated macrophages revealed that CCL24, a potent eosinophil attractant, was the most upregulated gene following culture with A suum larvae in vitro, and human eosinophils displayed even greater ability to adhere to, and trap, A suum larvae. These data suggest that immune serum-activated macrophages can recruit eosinophils to the site of infection, where they act in concert to immobilize tissue-migrating Ascaris larvae.
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Affiliation(s)
- Gillian Coakley
- Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Beatrice Volpe
- Global Health Institute, Swiss Federal Institute of Technology, Lausanne, Switzerland
| | - Tiffany Bouchery
- Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, Australia.,Global Health Institute, Swiss Federal Institute of Technology, Lausanne, Switzerland
| | - Kathleen Shah
- Global Health Institute, Swiss Federal Institute of Technology, Lausanne, Switzerland
| | - Alana Butler
- Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Peter Geldhof
- Department of Virology, Parasitology and Immunology, Laboratory of Parasitology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Mark Hatherill
- Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Cape Town, South Africa
| | - William G C Horsnell
- Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Cape Town, South Africa.,Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK
| | - Julia Esser-von Bieren
- Global Health Institute, Swiss Federal Institute of Technology, Lausanne, Switzerland.,Center of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich, Munich, Germany
| | - Nicola Laraine Harris
- Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, Australia.,Global Health Institute, Swiss Federal Institute of Technology, Lausanne, Switzerland
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Dana D, Vlaminck J, Ayana M, Tadege B, Mekonnen Z, Geldhof P, Levecke B. Evaluation of copromicroscopy and serology to measure the exposure to Ascaris infections across age groups and to assess the impact of 3 years of biannual mass drug administration in Jimma Town, Ethiopia. PLoS Negl Trop Dis 2020; 14:e0008037. [PMID: 32282815 PMCID: PMC7179930 DOI: 10.1371/journal.pntd.0008037] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 04/23/2020] [Accepted: 01/08/2020] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND The scientific community has recently summarized the desired characteristics for diagnostic tools across the different phases of a soil-transmitted helminth (STH) mass drug administration (MDA) program. Although serology meets some of the desired criteria, there is a scarcity of data on baseline serological profiles in human populations, both prior to and during MDA programs. METHODS In this study, we compared the copromicroscopic and the serological infection profiles in 600 school-aged children (SAC) and 600 adults at the advent of the MDA program in Jimma Town, Ethiopia. The serological profiles were examined by two ELISAs that measure IgG4 responses to the Ascaris suum haemoglobin antigen (AsHb) and a somatic extract of lung stage larvae (AsLungL3). Three years into the MDA program, we sampled another group of 600 SAC from the same schools to assess the reduction in prevalence and intensity of Ascaris infections measured by copromicroscopy and serology. PRINCIPAL FINDINGS Prior to the start of MDA, copromicroscopy revealed an Ascaris prevalence of 31.0% and a mean fecal egg count of 2,919 eggs per gram (EPG) in SAC. Following three years of biannual treatment, the prevalence reduced to 13.2% (57.8% reduction) and the mean fecal egg count to 1,513 EPG (48.1% reduction). This reduction was also reflected in the serological results. The seroprevalence reduced with 40.9% and 27.4% and the mean optical density ratio reduced with 44.2% and 38.2% as measured by the AsHb or AsLungL3 ELISA respectively. We also showed that, despite a decreasing coproprevalence, seroprevalence to Ascaris increased with age. CONCLUSIONS This study is the first to provide IgG4 response profiles of an endemic population to two different A. suum antigens. The results suggest that exposure to the infectious stages of Ascaris reaches beyond SAC alone. Furthermore, it highlights the possible use of serological assays to monitor changes in STH exposure during MDA programs.
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Affiliation(s)
- Daniel Dana
- School of Laboratory Science, Faculty of Health Science, Institute of Health, Jimma University, Jimma, Ethiopia
- Department of Virology, Parasitology and Immunology, Ghent University, Merelbeke, Belgium
| | - Johnny Vlaminck
- Department of Virology, Parasitology and Immunology, Ghent University, Merelbeke, Belgium
- * E-mail: (JV); (BL)
| | - Mio Ayana
- School of Laboratory Science, Faculty of Health Science, Institute of Health, Jimma University, Jimma, Ethiopia
| | - Bamlaku Tadege
- Department of Virology, Parasitology and Immunology, Ghent University, Merelbeke, Belgium
- School of Medicine, Hawassa University, Hawassa, Ethiopia
| | - Zeleke Mekonnen
- School of Laboratory Science, Faculty of Health Science, Institute of Health, Jimma University, Jimma, Ethiopia
| | - Peter Geldhof
- Department of Virology, Parasitology and Immunology, Ghent University, Merelbeke, Belgium
| | - Bruno Levecke
- Department of Virology, Parasitology and Immunology, Ghent University, Merelbeke, Belgium
- * E-mail: (JV); (BL)
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. N, Irawati N, Darwin E, Lipoeto NI. Relationship Between Interleukin-10, Cholesterol and Blood Glucose Levels in Geohelminth Positive Adolescents and Adults. JOURNAL OF MEDICAL SCIENCES 2019. [DOI: 10.3923/jms.2020.18.23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
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Amoani B, Adu B, Frempong MT, Sarkodie-Addo T, Victor Nuvor S, Abu EK, Harrison LM, Cappello M, Gyan B, Wilson MD. Cytokine profiles of Necator americanus and Plasmodium falciparum co-infected patients in rural Ghana. Cytokine X 2019; 1:100014. [PMID: 33604551 PMCID: PMC7885886 DOI: 10.1016/j.cytox.2019.100014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Revised: 08/21/2019] [Accepted: 08/28/2019] [Indexed: 12/20/2022] Open
Abstract
Co-infection of hookworm with P. falciparum modulates blood parasitemia levels. Cytokine levels were higher in the parasite infected individuals. Serum eotaxin level correlate negatively with hookworm intensity. Deworming drug treatment alters cytokine profiles in hookworm infected subjects. Background Necator americanus (hookworm) and Plasmodium falciparum co-infections are common in endemic communities in rural Ghana. Human immune responses to P. falciparum and hookworm are complex, and the dynamics of cytokine levels and effector mediators are poorly understood. This study aimed to determine the effect of hookworm and P. falciparum co-infection on parasite intensities and cytokine profiles in individuals before and after deworming drug treatment. Methods In this cross-sectional study conducted in the Kintampo North Municipality of Ghana blood and stool samples were analyzed from 984 participants (aged 4–88 years). Stool samples were collected at baseline from all participants and examined for the presence of hookworm using the Kato-Katz method. Blood and stool samples were analysed again two weeks after albendazole treatment of hookworm infected individuals. Malaria parasitaemia was estimated by light microscopy and P. falciparum-specific 18S rRNA gene PCR method used for species identification. Serum levels of circulating cytokines interleukins -5, -10 (IL-5, IL-10), tumor necrosis factor [TNF]-α, and eotaxin [CCL11] were determined using ELISA based methods. Results Malaria parasitaemia was significantly reduced in hookworm and P. falciparum co-infected individuals (p = 0.0018) while hookworm intensity was similar between groups. IL-10 level was significantly higher in the co-infected individuals (39.9 ± 12.2 pg/ml) compared to the single infected or the uninfected group (10.7 ± 7.6 mg/ml). IL-5 level was higher in the hookworm only infected individual. TNF-α levels were higher in all infected groups compared to the uninfected controls. CCL11 levels were significantly higher in subjects infected with hookworm only or co-infected with hookworm and P. falciparum. There was a significantly negative correlation (rs = −0.39, p = 0.021) between hookworm eggs per gram of stool and CCL11 levels in the group mono-infected with hookworm which was not affected by treatment. Treatment with albendazole led to a significant reduction of TNF-α (p = 0.041), IL-5 (p = 0.01) and IL-10 (p = 0.001) levels. Conclusion This study shows that in the absence of other helminths, co-infection of hookworm with P. falciparum may modulate blood parasitemia levels and cytokine responses. Data also show that deworming drug treatment alters these cytokine profiles in hookworm infected subjects. Future studies to elucidate the potential mechanisms underlying these observations should include an assessment of parasite specific cellular responses.
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Affiliation(s)
- Benjamin Amoani
- Department of Biomedical Science, College of Health Sciences, University of Cape Coast, Cape Coast, Ghana.,Department of Immunology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana.,Molecular Medicine Department, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Ghana
| | - Bright Adu
- Department of Immunology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana
| | - Margaret T Frempong
- Molecular Medicine Department, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Ghana
| | - Tracy Sarkodie-Addo
- Department of Immunology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana
| | - Samuel Victor Nuvor
- Department of Microbiology, College of Health Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Emmanuel Kwasi Abu
- Department of Optometry, College of Health Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Lisa M Harrison
- Partnerships for Global Health, Department of Pediatrics, Yale School of Medicine, Yale University, New Haven, CT, USA
| | - Michael Cappello
- Partnerships for Global Health, Department of Pediatrics, Yale School of Medicine, Yale University, New Haven, CT, USA
| | - Ben Gyan
- Department of Immunology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana
| | - Michael D Wilson
- Parasitology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana
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Chico ME, Vaca MG, Rodriguez A, Cooper PJ. Soil-transmitted helminth parasites and allergy: Observations from Ecuador. Parasite Immunol 2019; 41:e12590. [PMID: 30229947 PMCID: PMC6563446 DOI: 10.1111/pim.12590] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2018] [Revised: 09/07/2018] [Accepted: 09/12/2018] [Indexed: 01/01/2023]
Abstract
There is considerable interest as to potential protective effects of soil-transmitted helminths (STH) against allergy and allergic diseases. Here, we discuss findings of studies done of the effects of STH parasites on atopy and allergic diseases in Ecuador. While cross-sectional studies have consistently shown a reduced prevalence of allergen skin prick test (SPT) reactivity among infected schoolchildren, the removal of these infections by repeated deworming did not affect SPT prevalence over the short-term (ie, 12 months) but may have increased SPT prevalence over the long-term (ie, 15-17 years). In the case of allergic symptoms, cross-sectional studies have generally not shown associations with STH and intervention studies showed no impact on prevalence. However, a birth cohort suggested that early STH infections might reduce wheeze by 5 years. Allergic sensitization to Ascaris, however, explained a significant proportion of wheezing among rural schoolchildren. Studies of the effects of STH on immune and inflammatory responses indicated a potential role of STH in contributing to more robust regulation. The effects of STH on allergy are likely to be determined by history of exposure over the life-course and by interactions with a wide variety of other infectious and non-infectious factors.
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Affiliation(s)
- Martha E. Chico
- Fundación Ecuatoriana Para Investigación en SaludQuitoEcuador
| | - Maritza G. Vaca
- Fundación Ecuatoriana Para Investigación en SaludQuitoEcuador
| | - Alejandro Rodriguez
- Fundación Ecuatoriana Para Investigación en SaludQuitoEcuador
- Faculty of Epidemiology and Population HealthLondon School of Hygiene and Tropical MedicineLondonUK
- Facultad de Ciencias Medicas, de la Salud y la VidaUniversidad Internacional del EcuadorQuitoEcuador
| | - Philip J. Cooper
- Fundación Ecuatoriana Para Investigación en SaludQuitoEcuador
- Facultad de Ciencias Medicas, de la Salud y la VidaUniversidad Internacional del EcuadorQuitoEcuador
- Institute of Infection and ImmunitySt George's University of LondonLondonUK
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Cooper PJ, Chico ME, Vaca MG, Sandoval CA, Loor S, Amorim LD, Rodrigues LC, Barreto ML, Strachan DP. Effect of Early-Life Geohelminth Infections on the Development of Wheezing at 5 Years of Age. Am J Respir Crit Care Med 2019; 197:364-372. [PMID: 28957644 DOI: 10.1164/rccm.201706-1222oc] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
RATIONALE Exposures to geohelminths during gestation or early childhood may reduce risk of wheezing illness/asthma and atopy during childhood in tropical regions. OBJECTIVES To investigate the effect of maternal and early childhood geohelminths on development of wheeze/asthma and atopy during the first 5 years of life. METHODS A cohort of 2,404 neonates was followed to 5 years of age in a rural district in coastal Ecuador. Data on wheeze were collected by questionnaire and atopy was measured by allergen skin prick test reactivity to 10 allergens at 5 years. Stool samples from mothers and children were examined for geohelminths by microscopy. MEASUREMENTS AND MAIN RESULTS A total of 2,090 (86.9%) children were evaluated at 5 years. Geohelminths were observed in 45.5% of mothers and in 34.1% of children by 3 years. Wheeze and asthma were reported for 12.6% and 5.7% of children, respectively, whereas 14.0% had skin test reactivity at 5 years. Maternal geohelminths were associated with an increased risk of wheeze (adjusted odds ratio, 1.41; 95% confidence interval, 1.06-1.88), whereas childhood geohelminths over the first 3 years of life were associated with reduced risk of wheeze (adjusted odds ratio, 0.70; 95% confidence interval, 0.52-0.96) and asthma (adjusted odds ratio, 0.60; 95% confidence interval, 0.38-0.94) but not skin prick test reactivity. The effects on wheeze/asthma were greatest with later age of first infection, were observed only in skin test-negative children, but were not associated with parasite burden or specific geohelminths. CONCLUSIONS Although maternal exposures to geohelminths may increase childhood wheeze, childhood geohelminths during the first 3 years may provide protection through a nonallergic mechanism. Registered as an observational study (ISRCTN41239086).
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Affiliation(s)
- Philip J Cooper
- 1 Facultad de Ciencias Medicas, de la Salud y la Vida, Universidad Internacional del Ecuador, Quito, Ecuador.,2 Laboratorio de Investigaciones FEPIS, Quininde, Esmeraldas Province, Ecuador.,3 Institute of Infection and Immunity and
| | - Martha E Chico
- 2 Laboratorio de Investigaciones FEPIS, Quininde, Esmeraldas Province, Ecuador
| | - Maritza G Vaca
- 2 Laboratorio de Investigaciones FEPIS, Quininde, Esmeraldas Province, Ecuador
| | - Carlos A Sandoval
- 2 Laboratorio de Investigaciones FEPIS, Quininde, Esmeraldas Province, Ecuador
| | - Sofia Loor
- 2 Laboratorio de Investigaciones FEPIS, Quininde, Esmeraldas Province, Ecuador
| | - Leila D Amorim
- 4 Instituto de Saude Coletiva, Universidade Federal da Bahia, Salvador, Brazil; and
| | - Laura C Rodrigues
- 5 Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Mauricio L Barreto
- 4 Instituto de Saude Coletiva, Universidade Federal da Bahia, Salvador, Brazil; and
| | - David P Strachan
- 6 Population Health Research Institute, St. George's University of London, London, United Kingdom
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Co-expulsion of Ascaridia galli and Heterakis gallinarum by chickens. Int J Parasitol 2018; 48:1003-1016. [PMID: 30240707 DOI: 10.1016/j.ijpara.2018.05.014] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Revised: 05/28/2018] [Accepted: 05/31/2018] [Indexed: 01/01/2023]
Abstract
Worm expulsion is known to occur in mammalian hosts exposed to mono-species helminth infections, whilst this phenomenon is poorly described in avian hosts. Mono-species infections, however, are rather rare under natural circumstances. Therefore, we quantified the extent and duration of worm expulsion by chickens experimentally infected with both Ascaridia galli and Heterakis gallinarum, and investigated the accompanying humoral and cell-mediated host immune responses in association with population dynamics of the worms. Results demonstrated the strong co-expulsion of the two ascarid species in three phases. The expulsion patterns were characterized by non-linear alterations separated by species-specific time thresholds. Ascaridia galli burden decreased at a daily expulsion rate (e) of 4.3 worms up to a threshold of 30.5 days p.i., followed by a much lower second expulsion rate (e = 0.46), which resulted in almost, but not entirely, complete expulsion. Heterakis gallinarum was able to induce reinfection within the experimental period (9 weeks). First generation H. gallinarum worms were expelled at a daily rate of e = 0.8 worms until 36.4 days p.i., and thereafter almost no expulsion occurred. Data on both humoral and tissue-specific cellular immune responses collectively indicated that antibody production in chickens with multispecies ascarid infections is triggered by Th2 polarisation. Local Th2 immune responses and mucin-regulating genes are associated with the regulation of worm expulsion. In conclusion, the chicken host is able to eliminate the vast majority of both A. galli and H. gallinarum in three distinct phases. Worm expulsion was strongly associated with the developmental stages of the worms, where the elimination of juvenile stages was specifically targeted. A very small percentage of worms was nevertheless able to survive, reach maturity and induce reinfection if given sufficient time to complete their life cycle. Both humoral and local immune responses were associated with worm expulsion.
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Bwanika R, Kato CD, Welishe J, Mwandah DC. Cytokine profiles among patients co-infected with Plasmodium falciparum malaria and soil borne helminths attending Kampala International University Teaching Hospital, in Uganda. ALLERGY, ASTHMA, AND CLINICAL IMMUNOLOGY : OFFICIAL JOURNAL OF THE CANADIAN SOCIETY OF ALLERGY AND CLINICAL IMMUNOLOGY 2018; 14:10. [PMID: 29560020 PMCID: PMC5858126 DOI: 10.1186/s13223-018-0235-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Accepted: 02/06/2018] [Indexed: 01/22/2023]
Abstract
BACKGROUND Malaria and helminths share the same geographical distribution in tropical Africa. Studies of the interaction of helminth and malaria co-infection in humans have been few and are mainly epidemiological, with little information on cellular immune responses. This study aimed to determine Cytokine profiles among patients co-infected with Plasmodium falciparum malaria and soil borne helminth attending Kampala International University Teaching Hospital (KIU). METHODS A case control study of 240 patients were recruited at KIU teaching hospital. Patients with Plasmodium falciparum malaria were 55 (22.9%) and those with soil-borne helminths were 63 (26.3%). The controls were 89 (37.1%), while those co-infected with Plasmodium falciparum malaria and soil-borne helminths were 33 (13.8%). Cases were defined as having a positive blood smear for P. falciparum malaria, those with helminths or co-infections of the two. Negative controls were those with a negative blood smear for P. falciparum malaria and those with no stool parasitic infections. Patients presenting with signs and symptoms of malaria or those suspected of having helminths were recruited for the study. A panel of five cytokines (IFN-γ, TNF-α, IL-6, TGF-β and IL-10) were assayed from plasma samples in patients with and without Plasmodium falciparum malaria, patients with and without helminth, and then those co-infected with the two diseases diagnosis was done using thick blood smears stained with 10% Giemsa and stool examination was done following the Kato Katz technique following standard procedures. RESULTS The prevalence of Plasmodium falciparum malaria by sex was 28 (11.7%) and 27 (11.3%) in male and female respectively. The overall prevalence of soil borne helminth was 26.3%, and among those harbouring helminths, 13.8% were co-infected with Plasmodium falciparum. Cytokine levels significantly differed across Plasmodium falciparum malaria, soil borne helminth infected patients and health controls for IFN-γ (P = 0.023), IL-10 (P = 0.008) and TGF-β (P = 0.0001). Cytokine levels significantly differed across Plasmodium falciparum malaria, soil borne helminth infected patients and patients co-infected with Plasmodium falciparum malaria and soil borne helminth for IL-10 (P = 0.004), IL-6 (P = 0.011) and TGF-β (P = 0.003). CONCLUSION An up-regulation of IFN-γ during Plasmodium falciparum malaria and an up-regulation of IL-10 and TGF-β in soil borne helminth infections was demonstrated. We demonstrate that co-infections of Plasmodium falciparum and soil borne helminth lead to an up-regulation of IL-10 and IL-6 and a down-regulation of TGF-β.Trial registration No17/10-16.
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Affiliation(s)
- Richard Bwanika
- School of Biomedical Sciences, Department of Microbiology, Kampala International University, Western Campus, Ishaka, Box 71, Bushenyi, Uganda
| | - Charles D. Kato
- School of Biomedical Sciences, Department of Microbiology, Kampala International University, Western Campus, Ishaka, Box 71, Bushenyi, Uganda
- School of Bio-security, Biotechnical & Laboratory Sciences, College of Veterinary Medicine, Animal Resources & Bio-security, Makerere University, P.O Box 7062, Kampala, Uganda
| | - Johnson Welishe
- School of Biomedical Sciences, Department of Microbiology, Kampala International University, Western Campus, Ishaka, Box 71, Bushenyi, Uganda
- School of Bio-security, Biotechnical & Laboratory Sciences, College of Veterinary Medicine, Animal Resources & Bio-security, Makerere University, P.O Box 7062, Kampala, Uganda
| | - Daniel C. Mwandah
- School of Biomedical Sciences, Department of Microbiology, Kampala International University, Western Campus, Ishaka, Box 71, Bushenyi, Uganda
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Siedner MJ. Aging, Health, and Quality of Life for Older People Living With HIV in Sub-Saharan Africa: A Review and Proposed Conceptual Framework. J Aging Health 2017; 31:109-138. [PMID: 28831864 DOI: 10.1177/0898264317724549] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The number of people living with HIV (PLWH) over 50 years old in sub-Saharan Africa is predicted to triple in the coming decades, to 6-10 million. Yet, there is a paucity of data on the determinants of health and quality of life for older PLWH in the region. METHODS A review was undertaken to describe the impact of HIV infection on aging for PLWH in sub-Saharan Africa. RESULTS We (a) summarize the pathophysiology and epidemiology of aging with HIV in resource-rich settings, and (b) describe how these relationships might differ in sub-Saharan Africa, (c) propose a conceptual framework to describe determinants of quality of life for older PLWH, and (d) suggest priority research areas needed to ensure long-term gains in quality of life for PLWH in the region. CONCLUSIONS Differences in traditional, lifestyle, and envirnomental risk factors, as well as unique features of HIV epidemiology and care delivery appear to substantially alter the contribution of HIV to aging in sub-Saharan Africa. Meanwhile, unique preferences and conceptualizations of quality of life will require novel measurement and intervention tools. An expanded research and public health infrastructure is needed to ensure that gains made in HIV prevention and treamtent are translated into long-term benefits in this region.
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Affiliation(s)
- Mark J Siedner
- 1 Harvard Medical School, Boston, MA, USA.,2 Massachusetts General Hospital, Boston, MA, USA.,3 Mbarara University of Science and Technology, Mbarara, Uganda
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Bock CN, Babu S, Breloer M, Rajamanickam A, Boothra Y, Brunn ML, Kühl AA, Merle R, Löhning M, Hartmann S, Rausch S. Th2/1 Hybrid Cells Occurring in Murine and Human Strongyloidiasis Share Effector Functions of Th1 Cells. Front Cell Infect Microbiol 2017; 7:261. [PMID: 28676845 PMCID: PMC5476698 DOI: 10.3389/fcimb.2017.00261] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Accepted: 06/02/2017] [Indexed: 12/18/2022] Open
Abstract
Infections by the soil-transmitted threadworm Strongyloides stercoralis affect 30–100 million people worldwide, predominantly in tropic and sub-tropic regions. Here we assessed the T helper cell phenotypes in threadworm-infected patients and experimental murine infections with focus on CD4+ T cells co-expressing markers of Th2 and Th1 differentiation. We show that mice infected with the close relative S. ratti generate strong Th2 responses characterized by the expansion of CD4+ GATA-3+ cells expressing IL-4/-5/-13 in blood, spleen, gut-draining lymph nodes, lung and gut tissue. In addition to conventional Th2 cells, significantly increased frequencies of GATA-3+T-bet+ Th2/1-hybrid cells were detected in all organs and co-expressed Th2- and Th1-cytokines at intermediate levels. Assessing the phenotype of blood-derived CD4+ T cells from South Indian patients infected with S. stercoralis and local uninfected control donors we found that GATA-3 expressing Th2 cells were significantly increased in the patient cohort, coinciding with elevated eosinophil and IgE/IgG4 levels. A fraction of IL-4+CD4+ T cells simultaneously expressed IFN-γ hence displaying a Th2/1 hybrid phenotype. In accordance with murine Th2/1 cells, human Th2/1 cells expressed intermediate levels of Th2 cytokines. Contrasting their murine counterparts, human Th2/1 hybrids were marked by high levels of IFN-γ and rather low GATA-3 expression. Assessing the effector function of murine Th2/1 cells in vitro we found that Th2/1 cells were qualified for driving the classical activation of macrophages. Furthermore, Th2/1 cells shared innate, cytokine-driven effector functions with Th1 cells. Hence, the key findings of our study are that T helper cells with combined characteristics of Th2 and Th1 cells are integral to immune responses of helminth-infected mice, but also occur in helminth-infected humans and we suggest that Th2/1 cells are poised for the instruction of balanced immune responses during nematode infections.
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Affiliation(s)
- Cristin N Bock
- Department of Veterinary Medicine, Institute of Immunology, Freie Universität BerlinBerlin, Germany
| | - Subash Babu
- National Institutes of Health-NIRT-International Center for Excellence in ResearchChennai, India.,Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of HealthBethesda, MD, United States
| | - Minka Breloer
- Section for Molecular Biology and Immunology, Bernhard Nocht Institute for Tropical MedicineHamburg, Germany
| | - Anuradha Rajamanickam
- National Institutes of Health-NIRT-International Center for Excellence in ResearchChennai, India
| | - Yukhti Boothra
- National Institutes of Health-NIRT-International Center for Excellence in ResearchChennai, India
| | - Marie-Luise Brunn
- Section for Molecular Biology and Immunology, Bernhard Nocht Institute for Tropical MedicineHamburg, Germany
| | - Anja A Kühl
- Medical Department, Division of Gastroenterology, Infectiology and Rheumatology/Research Center ImmunoSciences, Charité-University Medicine BerlinBerlin, Germany
| | - Roswitha Merle
- Department of Veterinary Medicine, Institute for Veterinary Epidemiology and Biostatistics, Freie Universität BerlinBerlin, Germany
| | - Max Löhning
- Experimental Immunology, Department of Rheumatology and Clinical Immunology, Charité-University Medicine BerlinBerlin, Germany.,Pitzer Laboratory of Osteoarthritis Research, German Rheumatism Research Center (DRFZ), Leibniz InstituteBerlin, Germany
| | - Susanne Hartmann
- Department of Veterinary Medicine, Institute of Immunology, Freie Universität BerlinBerlin, Germany
| | - Sebastian Rausch
- Department of Veterinary Medicine, Institute of Immunology, Freie Universität BerlinBerlin, Germany
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Current progress toward vaccine and passive immunization approaches for Strongyloides spp. Immunol Lett 2016; 180:17-23. [DOI: 10.1016/j.imlet.2016.10.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2016] [Revised: 10/11/2016] [Accepted: 10/14/2016] [Indexed: 02/02/2023]
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IL-9 and Th9 in parasite immunity. Semin Immunopathol 2016; 39:29-38. [DOI: 10.1007/s00281-016-0606-9] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Accepted: 11/08/2016] [Indexed: 10/20/2022]
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Immune Profile of Honduran Schoolchildren with Intestinal Parasites: The Skewed Response against Geohelminths. J Parasitol Res 2016; 2016:1769585. [PMID: 27882241 PMCID: PMC5108857 DOI: 10.1155/2016/1769585] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2016] [Accepted: 10/10/2016] [Indexed: 01/18/2023] Open
Abstract
Soil-transmitted helminth infections typically induce a type-2 immune response (Th2), but no immunoepidemiological studies have been undertaken in Honduras, an endemic country where the main control strategy is children's annual deworming. We aimed to characterize the immune profile of Honduran schoolchildren harbouring these parasitoses. Demographic and epidemiological data were obtained through a survey; nutritional status was assessed through anthropometry; intestinal parasites were diagnosed by formol-ether and Kato-Katz; and blood samples were collected to determine immunological markers including Th1/Th2 cytokines, IgE, and eosinophil levels. A total of 225 children participated in the study, all of whom had received deworming during the national campaign five months prior to the study. Trichuriasis and ascariasis prevalence were 22.2% and 20.4%, respectively. Stunting was associated with both age and trichuriasis, whereas ascariasis was associated with sex and household conditions. Helminth infections were strongly associated with eosinophilia and hyper-IgE as well as with a Th2-polarized response (increased levels of IL-13, IL-10, and IL4/IFN-γ ratios and decreased levels of IFN-γ). Pathogenic protozoa infections were associated with a Th1 response characterized by elevated levels of IFN-γ and decreased IL10/IFN-γ ratios. Even at low prevalence levels, STH infections affect children's nutrition and play a polarizing role in their immune system.
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Ross KM, Miller G, Culhane J, Grobman W, Simhan HN, Wadhwa PD, Williamson D, McDade T, Buss C, Entringer S, Adam E, Qadir S, Keenan-Devlin L, Leigh AKK, Borders A. Patterns of peripheral cytokine expression during pregnancy in two cohorts and associations with inflammatory markers in cord blood. Am J Reprod Immunol 2016; 76:406-414. [PMID: 27615067 DOI: 10.1111/aji.12563] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Accepted: 08/15/2016] [Indexed: 01/02/2023] Open
Abstract
PROBLEM Maternal inflammation undergoes adaptations during pregnancy, and excessive inflammation has been associated with adverse outcomes. One mechanism may be maternal inflammation transmission to the fetal compartment. Links between maternal pregnancy inflammation and fetal inflammation are poorly characterized. METHOD Principal components analysis was used to extract underlying inflammation components across cytokines (IFN-γ, IL-10, IL-13, IL-6, IL-8, TNF-α) in two pregnancy cohorts (SPAH N=87, MOMS N=539) assessed during the second and third trimesters. Links between maternal inflammation over pregnancy and fetal (cord blood) inflammation were assessed. RESULTS Substantial cytokine rank-order stability was observed in both cohorts, β's range .47-.96, P's <.001. Two consistent inflammatory components were extracted: a pro-inflammatory (IL-10, IL-6, IL-8, TNF-α, IFN-γ) component and anti-inflammatory (IL-13) component. Higher maternal pro-inflammatory and lower anti-inflammatory indices during pregnancy were associated with higher cord blood inflammation, P's>.04. CONCLUSION Maternal inflammation indices over pregnancy were associated with inflammation in cord blood at birth. Results have implications for understanding pregnancy inflammatory processes and how maternal inflammation may be transmitted to fetal circulation.
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Affiliation(s)
- Kharah MacKenzie Ross
- Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA.
| | - Gregory Miller
- Department of Psychology, Northwestern University, Evanston, IL, USA.,Institute for Policy Research, Northwestern University, Evanston, IL, USA
| | - Jennifer Culhane
- Division of Adolescent Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.,Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - William Grobman
- Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.,Center for Healthcare Studies, Institute for Public Health and Medicine, Chicago, IL, USA
| | - Hyagriv N Simhan
- Division of Maternal-Fetal Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.,Division of Obstetrical Services, Magee Women's Hospital, Pittsburgh, PA, USA
| | - Pathik D Wadhwa
- UCI Development, Health and Disease Research Program, University of California Irvine, Irvine, CA, USA
| | - Douglas Williamson
- Department of Psychiatry and Behavioral Services, Duke University, Durham, NC, USA
| | - Thomas McDade
- Institute for Policy Research, Northwestern University, Evanston, IL, USA.,Department of Anthropology, Northwestern University, Evanston, IL, USA
| | - Claudia Buss
- UCI Development, Health and Disease Research Program, University of California Irvine, Irvine, CA, USA.,Charite Universitätsmedizin Berlin, Berlin, Germany
| | - Sonja Entringer
- UCI Development, Health and Disease Research Program, University of California Irvine, Irvine, CA, USA.,Charite Universitätsmedizin Berlin, Berlin, Germany
| | - Emma Adam
- Institute for Policy Research, Northwestern University, Evanston, IL, USA.,School of Education and Social Policy, Northwestern University, Evanston, IL, USA
| | - Sameen Qadir
- Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA
| | - Lauren Keenan-Devlin
- Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, NorthShore University Health System, Evanston, IL, USA
| | - Adam K K Leigh
- Department of Psychology, Northwestern University, Evanston, IL, USA
| | - Ann Borders
- Center for Healthcare Studies, Institute for Public Health and Medicine, Chicago, IL, USA.,Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.,Department of Obsetrics and Gynecology, Division of Maternal Fetal Medicine, NorthShore University Health System, University of Chicago Pritzker School of Medicine, Evanston, IL, USA
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Genser B, Fischer JE, Figueiredo CA, Alcântara-Neves N, Barreto ML, Cooper PJ, Amorim LD, Saemann MD, Weichhart T, Rodrigues LC. Applied immuno-epidemiological research: an approach for integrating existing knowledge into the statistical analysis of multiple immune markers. BMC Immunol 2016; 17:11. [PMID: 27206492 PMCID: PMC4875650 DOI: 10.1186/s12865-016-0149-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2015] [Accepted: 05/08/2016] [Indexed: 01/07/2023] Open
Abstract
Background Immunologists often measure several correlated immunological markers, such as concentrations of different cytokines produced by different immune cells and/or measured under different conditions, to draw insights from complex immunological mechanisms. Although there have been recent methodological efforts to improve the statistical analysis of immunological data, a framework is still needed for the simultaneous analysis of multiple, often correlated, immune markers. This framework would allow the immunologists’ hypotheses about the underlying biological mechanisms to be integrated. Results We present an analytical approach for statistical analysis of correlated immune markers, such as those commonly collected in modern immuno-epidemiological studies. We demonstrate i) how to deal with interdependencies among multiple measurements of the same immune marker, ii) how to analyse association patterns among different markers, iii) how to aggregate different measures and/or markers to immunological summary scores, iv) how to model the inter-relationships among these scores, and v) how to use these scores in epidemiological association analyses. We illustrate the application of our approach to multiple cytokine measurements from 818 children enrolled in a large immuno-epidemiological study (SCAALA Salvador), which aimed to quantify the major immunological mechanisms underlying atopic diseases or asthma. We demonstrate how to aggregate systematically the information captured in multiple cytokine measurements to immunological summary scores aimed at reflecting the presumed underlying immunological mechanisms (Th1/Th2 balance and immune regulatory network). We show how these aggregated immune scores can be used as predictors in regression models with outcomes of immunological studies (e.g. specific IgE) and compare the results to those obtained by a traditional multivariate regression approach. Conclusion The proposed analytical approach may be especially useful to quantify complex immune responses in immuno-epidemiological studies, where investigators examine the relationship among epidemiological patterns, immune response, and disease outcomes. Electronic supplementary material The online version of this article (doi:10.1186/s12865-016-0149-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Bernd Genser
- Instituto de Saúde Coletiva, Federal University of Bahia, Rua Basílio da Gama, s/n - Canela, Salvador, BA, 40110-040, Brazil. .,Mannheim Institute of Public Health, Social and Preventive Medicine, University of Heidelberg, Heidelberg, Germany.
| | - Joachim E Fischer
- Mannheim Institute of Public Health, Social and Preventive Medicine, University of Heidelberg, Heidelberg, Germany
| | - Camila A Figueiredo
- Instituto de Ciências da Saúde, Federal University of Bahia, Salvador, Brazil
| | | | - Mauricio L Barreto
- Instituto de Saúde Coletiva, Federal University of Bahia, Rua Basílio da Gama, s/n - Canela, Salvador, BA, 40110-040, Brazil.,Centro de Pesquisa Gonçalo Muniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil
| | - Philip J Cooper
- Institute of Infection and Immunity, St George's University of London, London, UK.,Centro de Investigación en Enfermedades Infecciosas y Crónicas, Pontificia Universidad Católica del Ecuador, Quito, Ecuador
| | - Leila D Amorim
- Instituto de Saúde Coletiva, Federal University of Bahia, Rua Basílio da Gama, s/n - Canela, Salvador, BA, 40110-040, Brazil.,Instituto de Matemática, Federal University of Bahia, Salvador, Brazil
| | - Marcus D Saemann
- Clinical Division of Nephrology, Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Thomas Weichhart
- Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria
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Takeuchi H, Khan AF, Yunus M, Hasan MI, Hawlader MDH, Takanashi S, Kano H, Zaman K, Chowdhury HR, Wagatsuma Y, Nakahara S, Iwata T. Anti-Ascaris immunoglobulin E associated with bronchial hyper-reactivity in 9-year-old rural Bangladeshi children. Allergol Int 2016; 65:141-146. [PMID: 26666493 DOI: 10.1016/j.alit.2015.07.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2015] [Revised: 06/17/2015] [Accepted: 07/04/2015] [Indexed: 10/23/2022] Open
Abstract
BACKGROUND Studies have addressed the immunomodulatory effects of helminths and their protective effects upon asthma. However, anti-Ascaris IgE has been reported to be associated with an increased risk of asthma symptoms. We examined the association between serum levels of anti-Ascaris IgE and bronchial hyper-responsiveness (BHR) in children living in rural Bangladesh. METHODS Serum anti-Ascaris IgE level was measured and the BHR test done in 158 children aged 9 years selected randomly from a general population of 1705 in the Matlab Health and Demographic Surveillance Area of the International Centre for Diarrhoeal Disease Research, Bangladesh. We investigated wheezing symptoms using a questionnaire from the International Study of Asthma and Allergies in Childhood. BHR tests were successfully done on 152 children (108 'current wheezers'; 44 'never-wheezers'). We examined the association between anti-Ascaris IgE level and wheezing and BHR using multiple logistic regression analyses. RESULTS Of 108 current-wheezers, 59 were BHR-positive; of 44 never-wheezers, 32 were BHR-negative. Mean anti-Ascaris IgE levels were significantly higher (12.51 UA/ml; 95% confidence interval (CI), 9.21-17.00) in children with current wheezing with BHR-positive than in those of never-wheezers with BHR-negative (3.89; 2.65-5.70; t test, p < 0.001). A BHR-positive test was independently associated with anti-Ascaris IgE levels with an odds ratio (OR) = 7.30 [95% CI, 2.28-23.33], p = 0.001 when adjusted for total IgE, anti-Dermatophagoides pteronyssinus IgE, pneumonia history, parental asthma, Trichuris infection, forced expiratory volume in one second, eosinophilic leukocyte count, and sex. CONCLUSIONS Anti-Ascaris IgE level is associated with an increased risk of BHR among 9-year-old rural Bangladeshi children.
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Dvorožňáková E, Dvorožňáková M, Šoltys J. Heavy metal intoxication compromises the host cytokine response in Ascaris Suum model infection. Helminthologia 2016. [DOI: 10.1515/helmin-2015-0063] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Summary
Lead (Pb), Cadmium (Cd) and Mercury (Hg) are recognized for their deleterious effect on the environment and immunity where subsequently compromised immune response affects the susceptibility to the potential parasitic infections. This study examined the host cytokine response after heavy metal intoxication (Pb, Cd, and Hg) and subsequent Ascaris suum infection in BALB/c mice. Pb modulated murine immune response towards the Th2 type of response (delineated by IL-5 and IL-10 cytokine production) what was also dominant for the outcome of A. suum infection. Chronic intoxication with Pb caused a more intensive development of the parasite infection. Cd stimulated the Th1 immune response what was associated with increase in IFN-γ production and reduction of larvae present in the liver of intoxicated mice. The larval burden was also low in mice intoxicated with Hg. This was probably not related to the biased Th1/Th2 type of immune response, but rather to the bad host conditions caused by mercury toxicity and high level of pro-cachectic cytokine TNF-α.
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Affiliation(s)
- E. Dvorožňáková
- Institute of Parasitology of the Slovak Academy of Sciences, Hlinkova 3, 040 01 Košice, Slovak Republic
| | - M. Dvorožňáková
- Eastern Slovak Institute for Cardiovascular Diseases, Košice, Slovak Republic
| | - J. Šoltys
- Institute of Parasitology of the Slovak Academy of Sciences, Hlinkova 3, 040 01 Košice, Slovak Republic
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Shalaby NM, Shalaby NM. Effect of Ascaris lumbricoides infection on T helper cell type 2 in rural Egyptian children. Ther Clin Risk Manag 2016; 12:379-85. [PMID: 27022269 PMCID: PMC4790525 DOI: 10.2147/tcrm.s94019] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Ascaris lumbricoides is a neglected parasite that induces changes in host immune response. This study is conducted to define the serum levels of tumor necrosis factor alpha (TNF-α), interleukin-4 (IL-4), and interleukin-5 (IL-5) in some Egyptian children and their relations to intensity of infection, age, and ascariasis symptoms. Stool samples were examined using formol-ether concentration and Kato-Katz thick smear techniques. Sera of 60 A. lumbricoides-infected children and 20 controls were tested by enzyme-linked immunosorbent assay. The mean sera concentrations of TNF-α, IL-4, and IL-5 were 7.41±2.5 pg/mL, 107.60±18.3 pg/mL, and 389.52±28.0 pg/mL, respectively. The controls had mean serum TNF-α 7.10±2.4 pg/mL, IL-4 25.49±2.6 pg/mL, and IL-5 88.76±22.7 pg/mL. The difference in the concentration of sera cytokines was statistically significant for IL-4 and IL-5 (P<0.01) between A. lumbricoides-infected children and controls. The intensity of infection correlated positively with IL-4 and IL-5 at r=0.959 and r=0.919, respectively. The concentrations of IL-4 and IL-5 correlated positively with the age at r=0.845 and r=0.934, respectively. Asthma and gastrointestinal tract upsets were correlated positively with IL-4 and IL-5. These data indicate that A. lumbricoides infection in our locality is associated with significantly high levels of IL-4 and IL-5.
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Affiliation(s)
- Naglaa M Shalaby
- Department of Parasitology, Faculty of Medicine, Mansoura, Egypt
| | - Nehad M Shalaby
- Mansoura University Children Hospital, Mansoura University, Mansoura, Egypt
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