|
1
|
Li L, Yao Y, Cao L, Le Y, Li X, Wang X, Zhang X, Li J, Zhang N, Jiang W, Gong P. RAGE-mediated intestinal pro-inflammatory responses triggered by Giardia duodenalis. Acta Trop 2025; 262:107529. [PMID: 39848554 DOI: 10.1016/j.actatropica.2025.107529] [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: 11/25/2024] [Revised: 01/12/2025] [Accepted: 01/13/2025] [Indexed: 01/25/2025]
Abstract
Giardia duodenalis is a waterborne zoonotic protozoan that causes gastrointestinal inflammation. Giardiasis and metabolic illnesses share features such as chronic inflammation and intestinal symptoms. Receptor for advanced glycation end products (RAGE) signaling plays a role in metabolic illnesses and intestinal inflammatory responses. The presence of protozoan viruses can influence host immunological responses triggered by protozoa. However, these effects of G. duodenalis remain unknown. In this study, mice treated with the RAGE inhibitor FPS-ZM1 showed more severe intestinal damage, including increased intestinal permeability and lesions, compared to that of the untreated group. Next, we found that G. duodenalis infection activated RAGE, leading to increased secretion of pro-inflammatory cytokines, including IL-1 β, IL-6, IL-12, TNF-α and IFN-γ in mouse intestinal epithelial cells. Notably, these pro-inflammatory responses were significantly higher in Giardiavirus (GLV)-free Giardia than those of GLV-containing Giardia, except for IFN-γ. Additionally, lactate dehydrogenase (LDH) release, GSDMD-N cleavage, and the morphological observation of pyroptosis were significantly higher in cells induced by GLV-free Giardia than those infected with GLV-carrying Giardia. Differences were also observed in the MAPK (p-JNK, p-38, p-ERK) and NF-κB pathway activation, as well as reactive oxygen species (ROS) levels, with higher activation in cells infected by GLV-free Giardia, and the ROS was involved in the regulation of p38 MAPK and JNK activation. These findings reveal the potential of RAGE as a target for developing vaccines or drugs, suggesting the differences in the regulation of host immune responses induced by GLV-free Giardia or GLV-containing Giardia, providing new insights for the prevention and treatment of giardiasis.
Collapse
Affiliation(s)
- Lu Li
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis and College of Veterinary Medicine, Jilin University, Changchun, 130062, China
| | - Yuxuan Yao
- College of Animal Sciences, Jilin University, Changchun, 130062, China
| | - Lili Cao
- Jilin Academy of Animal Husbandry and Veterinary Medicine, Changchun, 130062, China
| | - Yukun Le
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis and College of Veterinary Medicine, Jilin University, Changchun, 130062, China
| | - Xin Li
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis and College of Veterinary Medicine, Jilin University, Changchun, 130062, China
| | - Xiaocen Wang
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis and College of Veterinary Medicine, Jilin University, Changchun, 130062, China
| | - Xichen Zhang
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis and College of Veterinary Medicine, Jilin University, Changchun, 130062, China
| | - Jianhua Li
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis and College of Veterinary Medicine, Jilin University, Changchun, 130062, China
| | - Nan Zhang
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis and College of Veterinary Medicine, Jilin University, Changchun, 130062, China
| | - Weina Jiang
- Department of Pathology, Qingdao Municipal Hospital, Qingdao, Shandong Province, 266071, China
| | - Pengtao Gong
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis and College of Veterinary Medicine, Jilin University, Changchun, 130062, China.
| |
Collapse
|
|
2
|
Klimczak S, Packi K, Rudek A, Wenclewska S, Kurowski M, Kurczabińska D, Śliwińska A. The Influence of the Protozoan Giardia lamblia on the Modulation of the Immune System and Alterations in Host Glucose and Lipid Metabolism. Int J Mol Sci 2024; 25:8627. [PMID: 39201314 PMCID: PMC11354543 DOI: 10.3390/ijms25168627] [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: 06/10/2024] [Revised: 07/28/2024] [Accepted: 08/01/2024] [Indexed: 09/02/2024] Open
Abstract
Giardia lamblia, the cause of giardiasis, significantly impacts patients with metabolic disorders related to insulin resistance (IR). Both giardiasis and metabolic disorders share elements such as chronic inflammation and intestinal dysbiosis, which substantially affect the metabolic and cytokine profiles of patients. This review discusses the mechanisms of virulence of G. lamblia, its influence on the immune system, and its association with metabolic disorders. The review aims to show how G. lamblia invasion acts on the immune system and the glucose and lipid metabolism. Key findings reveal that G. lamblia infection, by disrupting intestinal permeability, alters microbiota composition and immune responses, potentially impairing metabolic status. Future research should focus on elucidating the specific mechanisms by which G. lamblia influences the metabolism, exploring the long-term consequences of chronic infection, and developing targeted therapeutic strategies that include both parasitic and metabolic aspects. These insights underscore the need for a multidisciplinary approach to the treatment of giardiasis in patients with metabolic disorders.
Collapse
Affiliation(s)
- Sylwia Klimczak
- Department of Nucleic Acid Biochemistry, Medical University of Lodz, 92-213 Lodz, Poland
- AllerGen Center of Personalized Medicine, 97-300 Piotrkow Trybunalski, Poland
| | - Kacper Packi
- AllerGen Center of Personalized Medicine, 97-300 Piotrkow Trybunalski, Poland
| | - Alicja Rudek
- AllerGen Center of Personalized Medicine, 97-300 Piotrkow Trybunalski, Poland
| | - Sylwia Wenclewska
- Diabetology and Internal Medicine Department, Provincial Hospital in Sieradz, 98-200 Sieradz, Poland
| | - Marcin Kurowski
- Department of Immunology and Allergy, Medical University of Lodz, 92-213 Lodz, Poland
| | | | - Agnieszka Śliwińska
- Department of Nucleic Acid Biochemistry, Medical University of Lodz, 92-213 Lodz, Poland
| |
Collapse
|
|
3
|
de Queiroz AA, França EL, Gadenz GRB, Dalcin LDL, Fujimori M, França DCH, Gomes MA, Honorio-França AC. Correlation between Melatonin and Colostral Regulatory T Cells in Giardia lamblia Infection. Biomolecules 2024; 14:744. [PMID: 39062459 PMCID: PMC11275092 DOI: 10.3390/biom14070744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 06/15/2024] [Accepted: 06/18/2024] [Indexed: 07/28/2024] Open
Abstract
Giardiasis is a parasitic disease caused by Giardia lamblia (G. lamblia) that affects people worldwide. Still, few studies report on the immunoregulatory effects of the biomolecules of colostrum during interactions with G. lamblia. This study aimed to assess the concentrations of melatonin and cortisol hormones, the percentage of Treg cells, and the levels of cytokines IL-10 and TGF-β in colostrum from mothers who tested positive for the parasite. This cross-sectional study analyzed colostrum samples from 25 puerperal. The samples were tested using an ELISA to determine if they were seropositive for G. lamblia and the type of antibody present (IgM and IgG). Based on the results, the samples were divided into three groups: a control group (N = 10) with no reaction to either IgM or IgG, a group seropositive for IgG (IgG+/IgM-; N = 8), and a group seropositive for IgM (IgM+/IgG-; N = 7). The concentrations of melatonin and cortisol were measured using the ELISA method. Additionally, cytokines IL-10 and TGF-β and immunophenotyping were analyzed using flow cytometry. In the group that tested positive for IgM anti-G. lamblia, the concentration of melatonin was lower. However, in the colostrum from mothers who tested positive for IgG anti-G. lamblia, the level of this hormone had increased. The cortisol levels were similar between the groups, regardless of seropositivity. There was a higher percentage of Treg cells in the colostrum from mothers who tested positive for IgM anti-G. lamblia. TGF-β levels also increased in the colostrum of mothers who tested positive for IgM anti-G. lamblia. In the seronegative group for G. lamblia, there was a positive correlation between melatonin concentration and the percentage of Treg cells. These data suggest that the increase in regulatory cells and cytokines and the reduction in melatonin in colostrum from mothers with recent giardia infection may contribute to the evolution and manifestation of the disease.
Collapse
Affiliation(s)
- Adriele Ataides de Queiroz
- Institute of Biological Sciences, Department of Parasitology, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil; (A.A.d.Q.); (M.A.G.)
- Institute of Biological and Health Sciences, Federal University of Mato Grosso, Barra do Garças 31270-901, Brazil; (E.L.F.); (G.R.B.G.); (L.D.L.D.); (M.F.); (D.C.H.F.)
| | - Eduardo Luzía França
- Institute of Biological and Health Sciences, Federal University of Mato Grosso, Barra do Garças 31270-901, Brazil; (E.L.F.); (G.R.B.G.); (L.D.L.D.); (M.F.); (D.C.H.F.)
| | - Gabriella Regina Borges Gadenz
- Institute of Biological and Health Sciences, Federal University of Mato Grosso, Barra do Garças 31270-901, Brazil; (E.L.F.); (G.R.B.G.); (L.D.L.D.); (M.F.); (D.C.H.F.)
| | - Letícia Damas Leão Dalcin
- Institute of Biological and Health Sciences, Federal University of Mato Grosso, Barra do Garças 31270-901, Brazil; (E.L.F.); (G.R.B.G.); (L.D.L.D.); (M.F.); (D.C.H.F.)
| | - Mahmi Fujimori
- Institute of Biological and Health Sciences, Federal University of Mato Grosso, Barra do Garças 31270-901, Brazil; (E.L.F.); (G.R.B.G.); (L.D.L.D.); (M.F.); (D.C.H.F.)
| | - Danielle Cristina Honorio França
- Institute of Biological and Health Sciences, Federal University of Mato Grosso, Barra do Garças 31270-901, Brazil; (E.L.F.); (G.R.B.G.); (L.D.L.D.); (M.F.); (D.C.H.F.)
| | - Maria Aparecida Gomes
- Institute of Biological Sciences, Department of Parasitology, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil; (A.A.d.Q.); (M.A.G.)
| | - Adenilda Cristina Honorio-França
- Institute of Biological and Health Sciences, Federal University of Mato Grosso, Barra do Garças 31270-901, Brazil; (E.L.F.); (G.R.B.G.); (L.D.L.D.); (M.F.); (D.C.H.F.)
| |
Collapse
|
|
4
|
Vicente B, Freitas AD, Freitas M, Midlej V. Systematic Review of Diagnostic Approaches for Human Giardiasis: Unveiling Optimal Strategies. Diagnostics (Basel) 2024; 14:364. [PMID: 38396402 PMCID: PMC10887752 DOI: 10.3390/diagnostics14040364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 01/30/2024] [Accepted: 01/31/2024] [Indexed: 02/25/2024] Open
Abstract
Giardiasis, caused by the protozoan Giardia intestinalis, affects around 400 million people worldwide, emphasizing the critical need for accurate diagnosis to enhance human health, especially in children. Prolonged giardiasis in childhood can lead to intellectual deficits and other complications. A variety of diagnostic tools, including microscopic, immunological, and molecular methods, are available for detecting G. intestinalis infection. Choosing the most suitable method can be challenging due to the abundance of options. This systematic review assesses the reliability and applicability of these diagnostic modalities. Utilizing the Dimensions and Wordart platforms for data analysis, we focus on relevant literature addressing diagnostic methods for human giardiasis. Microscopic techniques, particularly Ritchie's method, emerge as the primary choice, followed by enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). PCR's limited use is attributed to its high cost and infrastructure challenges in developing nations. In conclusion, our analysis supports microscopic methods as the gold standard for giardiasis diagnosis. However, in cases where symptoms persist despite a negative diagnosis, employing more sensitive diagnostic approaches is advisable.
Collapse
Affiliation(s)
- Bruno Vicente
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz—Fiocruz, Rio de Janeiro 21040-900, Brazil; (B.V.); (A.D.F.); (M.F.)
- Programa de Pós-Graduação em Biologia Celular e Molecular, Instituto Oswaldo Cruz—Fiocruz, Rio de Janeiro 21040-900, Brazil
| | - Anna De Freitas
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz—Fiocruz, Rio de Janeiro 21040-900, Brazil; (B.V.); (A.D.F.); (M.F.)
- Programa de Pós-Graduação em Biologia Parasitária, Instituto Oswaldo Cruz—Fiocruz, Rio de Janeiro 21040-900, Brazil
| | - Marcus Freitas
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz—Fiocruz, Rio de Janeiro 21040-900, Brazil; (B.V.); (A.D.F.); (M.F.)
| | - Victor Midlej
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz—Fiocruz, Rio de Janeiro 21040-900, Brazil; (B.V.); (A.D.F.); (M.F.)
| |
Collapse
|
|
5
|
España-Cueto S, Oliveira-Souto I, Salvador F, Goterris L, Treviño B, Sánchez-Montalvá A, Serre-Delcor N, Sulleiro E, Rodríguez V, Aznar ML, Bosch-Nicolau P, Espinosa-Pereiro J, Pou D, Molina I. Post-infectious irritable bowel syndrome following a diagnosis of traveller's diarrhoea: a comprehensive characterization of clinical and laboratory parameters. J Travel Med 2023; 30:taad030. [PMID: 36881659 DOI: 10.1093/jtm/taad030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 02/20/2023] [Accepted: 02/21/2023] [Indexed: 03/09/2023]
Abstract
BACKGROUND Prolonged or recurrent gastrointestinal symptoms may persist after acute traveller's diarrhoea (TD), even after adequate treatment of the primary cause. This study aims to describe the epidemiological, clinical and microbiological characteristics of patients with post-infectious irritable bowel syndrome (PI-IBS) after returning from tropical or subtropical areas. METHODS We conducted a retrospective study of patients presenting between 2009 and 2018 at the International Health referral centre in Barcelona with persistent gastrointestinal symptoms following a diagnosis of TD. PI-IBS was defined as the presence of persistent or recurrent gastrointestinal manifestations for at least 6 months after the diagnosis of TD, a negative stool culture for bacterial pathogens and a negative ova and parasite exam after targeted treatment. Epidemiological, clinical and microbiological variables were collected. RESULTS We identified 669 travellers with a diagnosis of TD. Sixty-eight (10.2%) of these travellers, mean age 33 years and 36 (52.9%) women, developed PI-IBS. The most frequently visited geographical areas were Latin America (29.4%) and the Middle East (17.6%), with a median trip duration of 30 days (IQR 14-96). A microbiological diagnosis of TD was made in 32 of these 68 (47%) patients, 24 (75%) of whom had a parasitic infection, Giardia duodenalis being the most commonly detected parasite (n = 20, 83.3%). The symptoms persisted for a mean of 15 months after diagnosis and treatment of TD. The multivariate analysis revealed that parasitic infections were independent risk factors for PI-IBS (OR 3.0, 95%CI 1.2-7.8). Pre-travel counselling reduced the risk of PI-IBS (OR 0.4, 95%CI 0.2-0.9). CONCLUSIONS In our cohort, almost 10% of patients with travellers' diarrhoea developed persistent symptoms compatible with PI-IBS. Parasitic infections, mainly giardiasis, seem to be associated with PI-IBS.
Collapse
Affiliation(s)
- Sergio España-Cueto
- International Health Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Vall d'Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain
- Infectious Diseases Department, Germans Trias i Pujol University Hospital, Badalona, Spain
- The Fight Infections Foundation, Badalona, Spain
| | - Inés Oliveira-Souto
- International Health Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Vall d'Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Fernando Salvador
- International Health Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Vall d'Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Lidia Goterris
- Department of Microbiology, Vall d'Hebron University Hospital and PROSICS, Barcelona, Spain
| | - Begoña Treviño
- International Health Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Vall d'Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Adrián Sánchez-Montalvá
- International Health Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Vall d'Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Núria Serre-Delcor
- International Health Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Vall d'Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Elena Sulleiro
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
- Department of Microbiology, Vall d'Hebron University Hospital and PROSICS, Barcelona, Spain
| | - Virginia Rodríguez
- Department of Microbiology, Vall d'Hebron University Hospital and PROSICS, Barcelona, Spain
| | - Maria Luisa Aznar
- International Health Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Vall d'Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Pau Bosch-Nicolau
- International Health Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Vall d'Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Juan Espinosa-Pereiro
- International Health Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Vall d'Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Diana Pou
- International Health Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Vall d'Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Israel Molina
- International Health Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Vall d'Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| |
Collapse
|
|
6
|
Giallourou N, Arnold J, McQuade ETR, Awoniyi M, Becket RVT, Walsh K, Herzog J, Gulati AS, Carroll IM, Montgomery S, Quintela PH, Faust AM, Singer SM, Fodor AA, Ahmad T, Mahfuz M, Mduma E, Walongo T, Guerrant RL, Balfour Sartor R, Swann JR, Kosek MN, Bartelt LA. Giardia hinders growth by disrupting nutrient metabolism independent of inflammatory enteropathy. Nat Commun 2023; 14:2840. [PMID: 37202423 PMCID: PMC10195804 DOI: 10.1038/s41467-023-38363-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 04/27/2023] [Indexed: 05/20/2023] Open
Abstract
Giardia lamblia (Giardia) is among the most common intestinal pathogens in children in low- and middle-income countries (LMICs). Although Giardia associates with early-life linear growth restriction, mechanistic explanations for Giardia-associated growth impairments remain elusive. Unlike other intestinal pathogens associated with constrained linear growth that cause intestinal or systemic inflammation or both, Giardia seldom associates with chronic inflammation in these children. Here we leverage the MAL-ED longitudinal birth cohort and a model of Giardia mono-association in gnotobiotic and immunodeficient mice to propose an alternative pathogenesis of this parasite. In children, Giardia results in linear growth deficits and gut permeability that are dose-dependent and independent of intestinal markers of inflammation. The estimates of these findings vary between children in different MAL-ED sites. In a representative site, where Giardia associates with growth restriction, infected children demonstrate broad amino acid deficiencies, and overproduction of specific phenolic acids, byproducts of intestinal bacterial amino acid metabolism. Gnotobiotic mice require specific nutritional and environmental conditions to recapitulate these findings, and immunodeficient mice confirm a pathway independent of chronic T/B cell inflammation. Taken together, we propose a new paradigm that Giardia-mediated growth faltering is contingent upon a convergence of this intestinal protozoa with nutritional and intestinal bacterial factors.
Collapse
Affiliation(s)
- Natasa Giallourou
- Division of Digestive Diseases, Department of Metabolism, Digestion, and Reproduction, Faculty of Medicine, Imperial College London, London, UK.
- Centre of Excellence in Biobanking and Biomedical Research, Molecular Medicine Research Center, University of Cyprus, Nicosia, Cyprus.
| | - Jason Arnold
- Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Department of Molecular Genetics and Microbiology, Duke Microbiome Center, Duke University School of Medicine, Durham, NC, 27710, USA
| | | | - Muyiwa Awoniyi
- Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Rose Viguna Thomas Becket
- Departments of Pediatrics and Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Kenneth Walsh
- Institute for Infectious Diseases and Global Health and the Division of Infectious Diseases, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Jeremy Herzog
- Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Ajay S Gulati
- Departments of Pediatrics and Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Ian M Carroll
- Department of Nutrition, Gillings School of Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Stephanie Montgomery
- Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | | | | | - Steven M Singer
- Department of Biology, Georgetown University, Washington, DC, USA
| | - Anthony A Fodor
- The University of North Carolina Charlotte, Department of Bioinformatics and Genomics, Charlotte, USA
| | - Tahmeed Ahmad
- International Center for Diarrheal Disease Research, Dhaka, Bangladesh
| | - Mustafa Mahfuz
- International Center for Diarrheal Disease Research, Dhaka, Bangladesh
| | - Esto Mduma
- Haydom Global Health Research Centre, Haydom Lutheran Hospital, Haydom, Tanzania
| | - Thomas Walongo
- Haydom Global Health Research Centre, Haydom Lutheran Hospital, Haydom, Tanzania
| | - Richard L Guerrant
- Division of Infectious Diseases and International Health, Department of Medicine, The University of Virginia Charlottesville, Charlottesville, VA, USA
| | - R Balfour Sartor
- Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Jonathan R Swann
- School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Margaret N Kosek
- Division of Infectious Diseases and International Health, Department of Medicine, The University of Virginia Charlottesville, Charlottesville, VA, USA
| | - Luther A Bartelt
- Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
- Institute for Infectious Diseases and Global Health and the Division of Infectious Diseases, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
- Department of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
| |
Collapse
|
|
7
|
Svendsen AT, Nielsen HL, Bytzer P, Coia JE, Engberg J, Holt HM, Lemming L, Lomborg S, Marmolin ES, Olesen BS, Andersen LP, Ethelberg S, Engsbro AL. The incidence of laboratory-confirmed cases of enteric pathogens in Denmark 2018: a national observational study. Infect Dis (Lond) 2023; 55:340-350. [PMID: 36868794 DOI: 10.1080/23744235.2023.2183253] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/05/2023] Open
Abstract
BACKGROUND Only a subset of enteric pathogens is under surveillance in Denmark, and knowledge on the remaining pathogens detected in acute gastroenteritis is limited. Here, we present the one-year incidence of all enteric pathogens diagnosed in Denmark, a high-income country, in 2018 and an overview of diagnostic methods used for detection. METHODS All 10 departments of clinical microbiology completed a questionnaire on test methods and provided 2018-data of persons with positive stool samples with Salmonella species, Campylobacter jejuni/coli, Yersinia enterocolitica, Aeromonas species, diarrheagenic Escherichia coli (Enteroinvasive (EIEC), Shiga toxin-producing (STEC), Enterotoxigenic (ETEC), Enteropathogenic (EPEC), and intimin-producing/attaching and effacing (AEEC)), Shigella species., Vibrio cholerae, norovirus, rotavirus, sapovirus, adenovirus, Giardia intestinalis, Cryptosporidium species, and Entamoeba histolytica. RESULTS Enteric bacterial infections were diagnosed with an incidence of 229.9 cases/100,000 inhabitants, virus had an incidence of 86/100,000 and enteropathogenic parasites of 12.5/100,000. Viruses constituted more than half of diagnosed enteropathogens for children below 2 years and elderly above 80 years. Diagnostic methods and algorithms differed across the country and in general PCR testing resulted in higher incidences compared to culture (bacteria), antigen-test (viruses), or microscopy (parasites) for most pathogens. CONCLUSIONS In Denmark, the majority of detected infections are bacterial with viral agents primarily detected in the extremes of ages and with few intestinal protozoal infections. Incidence rates were affected by age, clinical setting and local test methods with PCR leading to increased detection rates. The latter needs to be taken into account when interpreting epidemiological data across the country.
Collapse
Affiliation(s)
- Anna Tølbøll Svendsen
- Department of Medicine, Zealand University Hospital, Køge, Denmark.,Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.,Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen, Denmark
| | - Hans Linde Nielsen
- Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Peter Bytzer
- Department of Medicine, Zealand University Hospital, Køge, Denmark.,Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - John Eugenio Coia
- Department of Clinical Microbiology, Sydvestjysk Sygehus, Esbjerg, Denmark.,Department of Regional Health Research, University of Southern, Odense, Denmark
| | - Jørgen Engberg
- Department of Clinical Microbiology, Zealand University Hospital, Slagelse, Denmark
| | - Hanne Marie Holt
- Department of Clinical Microbiology, Odense University Hospital, Odense, Denmark
| | - Lars Lemming
- Department of Clinical Microbiology, Aarhus University Hospital, Denmark
| | - Steen Lomborg
- Department of Clinical Microbiology, Sygehus Sønderjylland, Aabenraa, Denmark
| | - Ea Sofie Marmolin
- Department of Clinical Microbiology, Sygehus Lillebælt, Vejle, Denmark
| | - Bente Scharvik Olesen
- Department of Clinical Microbiology, Copenhagen University Hospital Herlev, Copenhagen, Denmark
| | - Leif Percival Andersen
- Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Steen Ethelberg
- Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen, Denmark.,Department of Public Health, Global Health Section, University of Copenhagen, Copenhagen, Denmark
| | - Anne Line Engsbro
- Department of Clinical Microbiology, Zealand University Hospital, Slagelse, Denmark.,Copenhagen University Hospital Hvidovre, Copenhagen, Denmark
| |
Collapse
|
|
8
|
Kim SE. Functional Dyspepsia. HELICOBACTER PYLORI 2023:253-267. [DOI: 10.1007/978-981-97-0013-4_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
9
|
Dougherty M, Bartelt LA. Giardia and growth impairment in children in high-prevalence settings: consequence or co-incidence? Curr Opin Infect Dis 2022; 35:417-423. [PMID: 35980005 PMCID: PMC10373467 DOI: 10.1097/qco.0000000000000877] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
PURPOSE OF REVIEW Giardia is a common intestinal parasite worldwide, and infection can be associated with clear, and sometimes persistent symptomatology. However, in children in high-prevalence settings, it is most often not associated with or is perhaps even protective against acute diarrhea. Nonetheless, recent longitudinal studies in high-prevalence settings increasingly identify an association with long-term outcomes that has been difficult to discern. RECENT FINDINGS Recent studies have made progress in disentangling this apparent paradox. First, prospective, well characterized cohort studies have repeatedly identified associations between Giardia infection, gut function, and child growth. Second, experimental animal and in-vitro models have further characterized the biological plausibility that Giardia could impair intestinal function and subsequently child development through different pathways, depending upon biological and environmental factors. Finally, new work has shed light on the potential for Giardia conspiring with specific other gut microbes, which may explain discrepant findings in the literature, help guide future higher resolution analyses of this pathogen, and inform new opportunities for intervention. SUMMARY Recent prospective studies have confirmed a high, if not universal, prevalence of persistent Giardia infections in low-and-middle income countries associated with child-growth shortfalls and altered gut permeability. However, the predominance of subclinical infections limits understanding of the true clinical impact of endemic pediatric giardiasis, and global disease burdens remain uncalculated. Integrating the role of Giardia in multipathogen enteropathies and how nutritional, microbial, metabolic, and pathogen-strain variables influence Giardia infection outcomes could sharpen delineations between pathogenic and potentially beneficial attributes of this enigmatic parasite.
Collapse
Affiliation(s)
- Michael Dougherty
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill
- Rex Digestive Healthcare, UNC REX Healthcare, Raleigh
| | - Luther A. Bartelt
- Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| |
Collapse
|
|
10
|
Ibrahim HS, Salem AI, Ahmed NMAER, El-Taweel HA. Pre-and post-treatment evaluation of intestinal inflammation in Giardia and Blastocystis infected children: a community-based study. J Parasit Dis 2021; 45:1026-1033. [PMID: 34789986 DOI: 10.1007/s12639-021-01398-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 04/23/2021] [Indexed: 10/21/2022] Open
Abstract
Giardia intestinalis and Blastocystis hominis cause frequent infections in children in developing countries. However, the role of intestinal inflammation in their pathogenesis is still poorly understood. Faecal calprotectin (FC) level is used as an indicator of intestinal inflammation and neutrophil migration in the intestinal tract. The present study aimed to evaluate intestinal inflammation by measuring FC level among children infected with either G. intestinalis or B. hominis before and after treatment. Stool samples were collected from 282 children inhabiting a rural area in Egypt and examined microscopically for intestinal parasites. FC level was estimated in a group of children infected with G. intestinalis (n = 12) or B. hominis (n = 12) before and 3 weeks after receiving nitazoxanide (200 mg twice daily for 3 days) and compared to a control group (n = 18) of parasite-free children. Cases of mixed infection were excluded. Nitazoxanide cure rate was 83% in both infections with a remarkable reduction of infection intensity in uncured children. The difference in FC levels between infected children and controls was not statistically significant. Also, the difference between the pre- and post-treatment estimations was not statistically significant. Elevated levels were observed before treatment in three children (two infected with G. intestinalis and one with B. hominis) who displayed normal post-treatment levels. Although G. intestinalis and B. hominis infections appear to cause no remarkable intestinal inflammation, they may induce abnormally elevated FC levels in a subset of children.
Collapse
Affiliation(s)
- Heba Said Ibrahim
- Parasitology Department, Medical Research Institute, Alexandria University, Alexandria, Egypt
| | - Aziza Ibrahim Salem
- Parasitology Department, Medical Research Institute, Alexandria University, Alexandria, Egypt
| | | | - Hend Aly El-Taweel
- Parasitology Department, Medical Research Institute, Alexandria University, Alexandria, Egypt
| |
Collapse
|
|
11
|
Age and Giardia intestinalis Infection Impact Canine Gut Microbiota. Microorganisms 2021; 9:microorganisms9091862. [PMID: 34576757 PMCID: PMC8469385 DOI: 10.3390/microorganisms9091862] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 08/25/2021] [Accepted: 08/26/2021] [Indexed: 12/16/2022] Open
Abstract
Giardia intestinalis is a flagellated protozoan responsible for giardiosis (also called giardiasis in humans), the most prevalent and widespread parasitic infection in humans and mammals worldwide. The intestinal microbiota is highly diverse and any alteration in its composition may impact on the health of the host. While studies on the mouse model of giardiosis described the role of the gut microbiota in host susceptibility to infection by the parasite, little is known about the gut microbiota during natural infections in dogs and particularly in puppies. In this study, we monitored naturally G. intestinalis-infected puppies for 3 months and quantified cyst excretion every 2 weeks. All puppies remained subclinically infected during the sampling period as confirmed by fecal examination. In parallel, we performed 16S Illumina sequencing of fecal samples from the different time points to assess the impact of G. intestinalis infection on gut microbiota development of the puppies, as well as gut health markers of immunity such as fecal IgA and calprotectin. Sequencing results revealed that the canine fecal microbiota of Giardia-infected puppies becomes more complex and less diverse with increasing age. In addition, significant differences in the structure of the microbiota were observed between puppies with high and low Giardia cyst excretion. Chronic subclinical G. intestinalis infection appears to be associated with some detrimental structural changes in the gut microbiota. G. intestinalis-associated dysbiosis is characterized by an enrichment of facultative anaerobic, mucus-degrading, pro-inflammatory species and opportunistic pathogens, as well as a reduction of Lactobacillus johnsonii at specific time points. Calprotectin levels increased with age, suggesting the establishment of chronic low-grade inflammation in puppies. Further work is needed to demonstrate whether these alterations in the canine gut microbiota could lead to a dysbiosis-related disease, such as irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD).
Collapse
|
|
12
|
Dashti N, Zarebavani M. Probiotics in the management of Giardia duodenalis: an update on potential mechanisms and outcomes. Naunyn Schmiedebergs Arch Pharmacol 2021; 394:1869-1878. [PMID: 34324017 DOI: 10.1007/s00210-021-02124-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 07/07/2021] [Indexed: 10/20/2022]
Abstract
Giardia duodenalis is a common cause of infection in children and travelers. The most frequent symptom is diarrhea in these patients. G. duodenalis trophozoites use a highly specialized adhesive disc to attach the host intestinal epithelium to induce intestinal damages. Pathological features of the small intestine following giardiasis include villous atrophy; infiltration of granulocytes, lymphocytes, and plasma cells into the lamina propria; and nodular lymphoid hyperplasia. The disturbed intestinal microbiota has been observed in patients with giardiasis. Therefore, a growing body of evidence has emphasized restoring the gut microbiome by probiotics in giardiasis. This study aimed to review the literature to find the pathologic features of giardiasis and its relationship with imbalanced microbiota. Then, benefits of probiotics in giardiasis and their potential molecular mechanisms were discussed. It has been illustrated that using probiotics (e.g., Lactobacillus and Saccharomyces) can reduce the time of gastrointestinal symptoms and repair the damages, particularly in giardiasis. Probiotics' capability in restoring the composition of commensal microbiota may lead to therapeutic outcomes. According to preclinical and clinical studies, probiotics can protect against parasite-induced mucosal damages via increasing the antioxidant capacity, suppressing oxidative products, and regulating the systemic and mucosal immune responses. In addition, they can reduce the proportion of G. duodenalis load by directly targeting the parasite. They can destroy the cellular architecture of parasites and suppress the proliferation and growth of trophozoites via the production of some factors with anti-giardial features. Further researches are required to find suitable probiotics for the prevention and treatment of giardiasis.
Collapse
Affiliation(s)
- Nasrin Dashti
- Department of Clinical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
| | - Mitra Zarebavani
- Department of Clinical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
|
13
|
Pu X, Li X, Cao L, Yue K, Zhao P, Wang X, Li J, Zhang X, Zhang N, Zhao Z, Liang M, Gong P. Giardia duodenalis Induces Proinflammatory Cytokine Production in Mouse Macrophages via TLR9-Mediated p38 and ERK Signaling Pathways. Front Cell Dev Biol 2021; 9:694675. [PMID: 34336841 PMCID: PMC8319647 DOI: 10.3389/fcell.2021.694675] [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: 04/13/2021] [Accepted: 06/16/2021] [Indexed: 12/12/2022] Open
Abstract
Giardia duodenalis, also known as Giardia lamblia or Giardia intestinalis, is an important opportunistic, pathogenic, zoonotic, protozoan parasite that infects the small intestines of humans and animals, causing giardiasis. Several studies have demonstrated that innate immunity-associated Toll-like receptors (TLRs) are critical for the elimination of G. duodenalis; however, whether TLR9 has a role in innate immune responses against Giardia infection remains unknown. In the present study, various methods, including reverse transcriptase–quantitative polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay, immunofluorescence, inhibitor assays, and small-interfering RNA interference, were utilized to probe the role of TLR9 in mouse macrophage-mediated defenses against G. lamblia virus (GLV)–free or GLV-containing Giardia trophozoites. The results revealed that in G. duodenalis–stimulated mouse macrophages, the secretion of proinflammatory cytokines, including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and IL-12 p40, was enhanced, concomitant with the significant activation of TLR9, whereas silencing TLR9 attenuated the host inflammatory response. Notably, the presence of GLV exacerbated the secretion of host proinflammatory cytokines. Moreover, G. duodenalis stimulation activated multiple signaling pathways, including the nuclear factor κB p65 (NF-κB p65), p38, ERK, and AKT pathways, the latter three in a TLR9-dependent manner. Additionally, inhibiting the p38 or ERK pathway downregulated the G. duodenalis–induced inflammatory response, whereas AKT inhibition aggravated this process. Taken together, these results indicated that G. duodenalis may induce the secretion of proinflammatory cytokines by activating the p38 and ERK signaling pathways in a TLR9-dependent manner in mouse macrophages. Our in vitro findings on the mechanism underlying the TLR9-mediated host inflammatory response may help establish the foundation for an in-depth investigation of the role of TLR9 in the pathogenicity of G. duodenalis.
Collapse
Affiliation(s)
- Xudong Pu
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Xin Li
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Lili Cao
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China.,Department of Parasite, Jilin Academy of Animal Husbandry and Veterinary Medicine, Changchun, China
| | - Kaiming Yue
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Panpan Zhao
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Xiaocen Wang
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Jianhua Li
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Xichen Zhang
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Nan Zhang
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Zhiteng Zhao
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Min Liang
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Pengtao Gong
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| |
Collapse
|
|
14
|
Abstract
PURPOSE OF REVIEW Giardiasis remains a common cause of diarrhea and intestinal enteropathy globally. Here we give an overview of clinical treatment studies and discuss potential mechanisms and molecular targets for in-vitro testing of drug resistance. RECENT FINDINGS Giardia is a cause of disease both in diarrheal and nondiarrheal cases. The prevalence of treatment refractory giardiasis is increasing. Recent studies reveal 5-nitroimidazole refractory infection occurs in up to 50% of cases. Mechanisms of drug resistance are not known. Placebo controlled studies of drug efficacy, taking the self-limiting course of giardiasis into account, has not been reported. No randomized controlled trials of treatment of refractory infection have been performed the last 25 years. Based on the clinical studies reported, combination treatment with a 5-nitroimidazole and a benzimidazole is more effective than repeated courses of 5-nitroimidazole or monotherapies in refractory cases. Quinacrine is effective in refractory cases, but potentially severe side effects limit its use. SUMMARY A combination of a 5-nitroimidazole and albendazole or mebendazole, and quinacrine monotherapy, are rational choices in nitroimidazole refractory infections, but randomized controlled studies are needed. Further research into more recent clinical isolates is necessary to uncover mechanisms for the increase in metronidazole refractory giardiasis observed during the last decade.
Collapse
|
|
15
|
Capone D, Chigwechokha P, de los Reyes FL, Holm RH, Risk BB, Tilley E, Brown J. Impact of sampling depth on pathogen detection in pit latrines. PLoS Negl Trop Dis 2021; 15:e0009176. [PMID: 33651818 PMCID: PMC7954291 DOI: 10.1371/journal.pntd.0009176] [Citation(s) in RCA: 12] [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: 11/18/2020] [Revised: 03/12/2021] [Accepted: 01/25/2021] [Indexed: 01/03/2023] Open
Abstract
Wastewater based epidemiology (WBE) is increasingly used to provide decision makers with actionable data about community health. WBE efforts to date have primarily focused on sewer-transported wastewater in high-income countries, but at least 1.8 billion people in low- and middle-income countries (LMIC) use onsite sanitation systems such as pit latrines and septic tanks. Like wastewater, fecal sludges from such systems offer similar advantages in community pathogen monitoring and other epidemiological applications. To evaluate the distribution of enteric pathogens inside pit latrines-which could inform sampling methods for WBE in LMIC settings unserved by sewers-we collected fecal sludges from the surface, mid-point, and maximum-depth of 33 pit latrines in urban and peri-urban Malawi and analyzed the 99 samples for 20 common enteric pathogens via multiplex quantitative reverse transcription PCR. Using logistic regression adjusted for household population, latrine sharing, the presence of a concrete floor or slab, water source, and anal cleansing materials, we found no significant difference in the odds of detecting the 20 pathogens from the mid-point (adjusted odds ratio, aOR = 1.1; 95% confidence interval = 0.73, 1.6) and surface samples (aOR = 0.80, 95% CI = 0.54, 1.2) compared with those samples taken from the maximum depth. Our results suggest that, for the purposes of routine pathogen monitoring, pit latrine sampling depth does not strongly influence the odds of detecting enteric pathogens by molecular methods. A single sample from the pit latrines' surface, or a composite of surface samples, may be preferred as the most recent material contributed to the pit and may be easiest to collect.
Collapse
Affiliation(s)
- Drew Capone
- Civil and Environmental Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States of America
- 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
| | - Petros Chigwechokha
- Directorate of Research, Malawi University of Science and Technology, Blantyre, Malawi
| | - Francis L. de los Reyes
- Department of Civil, Construction, and Environmental Engineering, North Carolina State University, Raleigh, North Carolina, United States of America
| | - Rochelle H. Holm
- Centre of Excellence in Water and Sanitation, Mzuzu University, Mzuzu, Malawi
- Christina Lee Brown Envirome Institute, University of Louisville, Louisville, Kentucky, United States of America
| | - Benjamin B. Risk
- Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia, United States of America
| | - Elizabeth Tilley
- Department of Environmental Health, University of Malawi, Blantyre, Malawi
- Department of Sanitation, Water and Solid Waste for Development, Swiss Federal Institute of Aquatic Science and Technology, Duebendorf, Switzerland
| | - Joe Brown
- Civil and Environmental Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States of America
- 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
| |
Collapse
|
|
16
|
El-Gendy AML, Mohammed MAA, Ghallab MMI, Abdel Aziz MO, Ibrahim SM. Therapeutic Effect of Chitosan Nanoparticles and Metronidazole in Treatment of Experimentally Giardiasis Infected Hamsters. IRANIAN JOURNAL OF PARASITOLOGY 2021; 16:32-42. [PMID: 33786045 PMCID: PMC7988670 DOI: 10.18502/ijpa.v16i1.5509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Background: The present study aimed to assess the therapeutic effect of chitosan nanoparticles and metronidazole against Giardia lamblia as well as evaluate the efficacy of loading metronidazole on chitosan nanoparticles. Methods: This study was carried out at medical Parasitology Department, Faculty of Medicine, Zagazig University and Theodor Bilharz Research institute (TBRI) from February 2019 to February 2020 on 45 hamsters. They were divided into 5 groups 9 hamsters each: Group A non-infected hamsters, Group B infected control group, Group C, D and E infected with G. lamblia and treated with Chitosan nanoparticles (CsNPs), metronidazole (MTZ) and metronidazole-loaded chitosan nanoparticles (MTZ-CsNPs) respectively. Results: The highest percentage of reduction in the Giardia cyst and trophozoite counts were in group that received MTZ-CsNPs (94.69%, 94.29%). Lower percentages of reduction were recorded for MTZ treated group (90.15%, 89.52%) and CsNPs treated group (63.64%, 75.24%). Histopathological examination showed marked healing of intestinal mucosa after treatment with MTZ-CsNPs. Conclusion: CsNPs showed a therapeutic effect against Giardia infection in hamsters. Loading of metronidazole on chitosan nanoparticles enhanced therapeutic effect of both CsNPs as well as metronidazole.
Collapse
Affiliation(s)
| | | | | | - Marwa Omar Abdel Aziz
- Department of Medical Parasitology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | | |
Collapse
|
|
17
|
Multilocus Genotyping of Giardia duodenalis in Mostly Asymptomatic Indigenous People from the Tapirapé Tribe, Brazilian Amazon. Pathogens 2021; 10:pathogens10020206. [PMID: 33672794 PMCID: PMC7917967 DOI: 10.3390/pathogens10020206] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 02/01/2021] [Accepted: 02/08/2021] [Indexed: 02/06/2023] Open
Abstract
Little information is available on the occurrence and genetic variability of the diarrhoea-causing enteric protozoan parasite Giardia duodenalis in indigenous communities in Brazil. This cross-sectional epidemiological survey describes the frequency, genotypes, and risk associations for this pathogen in Tapirapé people (Brazilian Amazon) at four sampling campaigns during 2008–2009. Microscopy was used as a screening test, and molecular (PCR and Sanger sequencing) assays targeting the small subunit ribosomal RNA, the glutamate dehydrogenase, the beta-giardin, and the triosephosphate isomerase genes as confirmatory/genotyping methods. Associations between G. duodenalis and sociodemographic and clinical variables were investigated using Chi-squared test and univariable/multivariable logistic regression models. Overall, 574 individuals belonging to six tribes participated in the study, with G. duodenalis prevalence rates varying from 13.5–21.7%. The infection was positively linked to younger age and tribe. Infected children <15 years old reported more frequent gastrointestinal symptoms compared to adults. Assemblage B accounted for three out of four G. duodenalis infections and showed a high genetic diversity. No association between assemblage and age or occurrence of diarrhoea was demonstrated. These data indicate that the most likely source of infection was anthropic and that different pathways (e.g., drinking water) may be involved in the transmission of the parasite.
Collapse
|
|
18
|
Khedr SI, Mokhamer EHM, Hassan AA, El-Feki AS, Elkhodary GM, El-Gerbed MS. Psidium guajava Linn leaf ethanolic extract: In vivo giardicidal potential with ultrastructural damage, anti-inflammatory and antioxidant effects. Saudi J Biol Sci 2021; 28:427-439. [PMID: 33424326 PMCID: PMC7783632 DOI: 10.1016/j.sjbs.2020.10.026] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 10/17/2020] [Accepted: 10/18/2020] [Indexed: 12/03/2022] Open
Abstract
Introduction and aim Considering the magnitude of giardiasis problem, the side-effects of the used anti-giardia drugs and the resistance posed against them, the current study aimed to evaluate the in-vivo giardicidal effect of Psidium guajava leaf extract (PGLE). Methods For fulfilling this aim, five Swiss-albino mice groups were included; GI: non-infected, GII: Giardia-infected and non-treated, GIII: Giardia-infected and metronidazole-treated, GIV: Giardia-infected and PGLE-treated, and GV: Giardia-infected and treated with both metronidazole and PGLE. Treatment efficacy was assessed via; Giardia cyst viability and trophozoite count, trophozoite electron microscopic ultrastructure, duodenal histopathological scoring, immunohistochemistry for TNF-α and duodenal scanning electron microscopy. Moreover, mice serum liver enzymes, total bilirubin, albumin, lipid profile including; total cholesterol, HDL, LDL and triglycerides were assessed. Additionally, hepatic oxidative stress markers including; malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH) and superoxide dismutase (SOD) were measured. Results Results showed that PGLE whether alone or combined with metronidazole has induced significant trophozoite count reduction and major architectural changes. Duodenal histological improvement, and local protective anti-inflammatory effect were confirmed. PGLE has also helped in healing of Giardia-induced gut atrophy. Thus, offered a comprehensive therapy for both the pathogen and the resultant pathological sequalae. Serum markers showed favorable hepatoprotective effect. Total cholesterol, LDL and triglycerides levels were less in PGLE-treated group than in metronidazole-treated group. Hepatic oxidative stress markers revealed the promising extract antioxidant effect. This study highlights, the promising in-vivo giardicidal PGLE activity, that was comparable to metronidazole, thus, the extract would be an ideal strongly recommended treatment for giardiasis. When combined with metronidazole, the extract potentiated its therapeutic effect. Besides, having hepatoprotective, anti-inflammatory, and antioxidant properties, the extract can combat the major side effects of metronidazole therapy.
Collapse
Key Words
- ALT, alanine aminotransferase
- AST, aspartate aminotransferase
- Duodenal ultrastructure
- G. lamblia, Giardia lamblia
- GSH, reduced glutathione
- Giardia lamblia
- H&E, hematoxylin and eosin
- HDL, high-density lipoproteins
- LDL, low-density lipoproteins
- MDA, malondialdehyde
- MNZ, metronidazole
- NO, nitric oxide
- Nitric oxide
- PGLE, Psidium guajava Linn. leaf extract
- Psidium guajava leaf extract
- ROS, reactive oxygen species
- SEM, scanning electron microscopy
- SOD, superoxide dismutase enzyme
- Superoxide dismutase
- TEM, transmission electron microscopy
- TNF-α, tumor necrosis factor-alpha
- Tumor necrosis factor-α
Collapse
Affiliation(s)
- Safaa I. Khedr
- Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
- Corresponding author at: Medical Parasitology Department, El Mowasah Medical and Educational Complex, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
| | | | - Amal A.A. Hassan
- Department of Zoology, Faculty of Science, Damanhour University, Damanhour, Egypt
| | - Asmaa S. El-Feki
- Department of Zoology, Faculty of Science, Damanhour University, Damanhour, Egypt
| | - Gihan M. Elkhodary
- Department of Zoology, Faculty of Science, Damanhour University, Damanhour, Egypt
| | | |
Collapse
|
|
19
|
Garzon T, Valencia L, Dominguez V, Rascon L, Quintero J, Garibay-Escobar A, Enrique Robles-Zepeda R, Velazquez C. Differential antibody responses to Giardia lamblia strain variants expressing dissimilar levels of an immunogenic protein. Parasite Immunol 2020; 42:e12767. [PMID: 32594543 DOI: 10.1111/pim.12767] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Revised: 06/13/2020] [Accepted: 06/15/2020] [Indexed: 12/18/2022]
Abstract
AIMS Giardia lamblia is a protozoan parasite that causes giardiasis, one of the most common worldwide gastrointestinal diseases. For rational development of a Giardia vaccine, increasing our understanding of the host-Giardia interaction is crucial. In this study, we analysed the immunogenicity and antigenicity of two G lamblia strain variants [GS and GS-5G8 (+)], which express different levels of the variant-specific surface protein (VSP) 5G8 and also analysed the intestinal histological changes associated with Giardia infection. METHODS AND RESULTS We evaluated the antibody responses induced by G lamblia strains in infected, reinfected and immunized C3H/HeJ mice using ELISA, flow cytometry, Western blotting and histological analysis. Our results showed that G lamblia GS-5G8 (+) was more immunogenic and antigenic than the GS strain. The antibody response against the GS-5G8 (+) strain primarily recognized 5G8 protein. Serum antibody from infected and reinfected mice exhibited specific agglutination of trophozoites in vitro. GS-5G8 (+)-infected mice showed higher CD19+ infiltrating cell levels compared to GS-infected animals. CONCLUSION G lamblia strains with different expression levels of an immunogenic antigen (VSP 5G8) induce differential antibody responses. A better understanding of the immunogenic proteins of G lamblia will contribute to the rational development of an effective vaccine against this parasitic disease.
Collapse
Affiliation(s)
- Thania Garzon
- Department of Chemistry-Biology, University of Sonora, Hermosillo, Mexico
| | - Lourdes Valencia
- Department of Chemistry-Biology, University of Sonora, Hermosillo, Mexico
| | - Victor Dominguez
- Department of Chemistry-Biology, University of Sonora, Hermosillo, Mexico
| | - Lucila Rascon
- Department of Chemistry-Biology, University of Sonora, Hermosillo, Mexico
| | - Jael Quintero
- Health Science Department, University of Sonora, Obregon, Mexico
| | | | | | - Carlos Velazquez
- Department of Chemistry-Biology, University of Sonora, Hermosillo, Mexico
| |
Collapse
|
|
20
|
Pehlivanoğlu B, Ardeniz Ö, Hassoy H, Sezak M, Özdemir H, Ünal NG, Onay H, Doğanavşargil B. Gastrointestinal findings in 26 adults with common variable immunodeficiency: The fickle nature of the disease manifests in gastrointestinal biopsies. TURKISH JOURNAL OF GASTROENTEROLOGY 2020; 30:789-800. [PMID: 31530523 DOI: 10.5152/tjg.2019.18777] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND/AIMS The aim of the present study was to demonstrate the histopathological findings in gastrointestinal (GI) biopsies in adults with common variable immunodeficiency (CVID). MATERIALS AND METHODS A total of 172 GI biopsies of 26 patients with CVID obtained over a 16-year period were reevaluated. Findings were analyzed using descriptive analyzes and χ2 test. RESULTS Female-to-male ratio was 1.36. The median age at diagnosis was 36±13.94 (16-72) years. Chronic esophagitis was noted in 3 patients. The absence of plasma cells in the stomach, duodenum, and colon was observed in 16, 14, and 9 patients, respectively. Divergent results for the presence of plasma cells in concurrent stomach and duodenum samples were found in 11 (44%) patients. Nodular lymphoid hyperplasia (NLH) was notable in the duodenum (56%). The mean number of eosinophils in one high-power field was significantly higher in duodenal biopsies with NLH (27.21 vs. 14.37, p=0.002). Active inflammation was more prominent in the colon (91%) than in the stomach (65%) and duodenum (60%). Helicobacter pylori infection was found in 57.6%, including a case with persistent infection by the coccoid form. Celiac-like villous blunting and increased intraepithelial lymphocytes were seen in 40% and 24%, respectively. In addition, 23% had giardiasis associated with acute duodenitis and duodenal NLH (p<0.05). CONCLUSION CVID gastroenteropathy is a challenging entity, and due to the heterogeneity in the presence and distribution of plasma cells throughout the GI tract and diverse disease course, multiple concurrent biopsies may be needed for tissue diagnosis. Duodenal CVID may present with villous alterations and giardiasis, and NLH appears to be an important clue in the duodenum. The association between duodenal NLH and eosinophil infiltration deserves further investigation.
Collapse
Affiliation(s)
- Buçin Pehlivanoğlu
- Department of Pathology, Ege University School of Medicine, İzmir, Turkey
| | - Ömür Ardeniz
- Division of Immunology, Department of Internal Medicine, Ege University School of Medicine, İzmir, Turkey
| | - Hür Hassoy
- Department of Public Health, Ege University School of Medicine, İzmir, Turkey
| | - Murat Sezak
- Department of Pathology, Ege University School of Medicine, İzmir, Turkey
| | - Hafize Özdemir
- Department of Pathology, Ege University School of Medicine, İzmir, Turkey
| | - Nalan Gülşen Ünal
- Division of Gastroenterology, Department of Internal Medicine, Ege University School of Medicine, İzmir, Turkey
| | - Hüseyin Onay
- Department of Medical Genetics, Ege University School of Medicine, İzmir, Turkey
| | | |
Collapse
|
|
21
|
Associations between enteric pathogen carriage and height-for-age, weight-for-age and weight-for-height in children under 5 years old in urban Dhaka, Bangladesh. Epidemiol Infect 2020; 148:e39. [PMID: 32102708 PMCID: PMC7058651 DOI: 10.1017/s0950268820000369] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Nutritional factors and infectious agents may contribute to paediatric growth deficits in low- and middle-income countries; however, the contribution of enteric pathogens is only beginning to be understood. We analysed the stool from children <5 years old from an open cohort, cluster-randomised controlled trial of a point-of-collection water chlorinator in urban Bangladesh. We compared the presence/absence of 15 enteric pathogens detected via multiplex, molecular methods in the stool with concurrent Z-scores/Z-score cut-offs (−2 standard deviations (s.d.)) for height-for-age (HAZ/stunting), weight-for-age (WAZ/underweight) and weight-for-height (WHZ/wasting), adjusted for sociodemographic and trial-related factors, and measured caregiver-reported diarrhoea. Enteric pathogen prevalence in the stool was high (88% had ≥1 enteric pathogen, most commonly Giardia spp. (40%), Salmonella enterica (33%), enterotoxigenic E. coli (28%) and Shigella spp. (27%)) while reported 7-day diarrhoea prevalence was 6%, suggesting high subclinical infection rates. Many children were stunted (26%) or underweight (24%). Adjusted models suggested Giardia spp. detection was associated with lower HAZ (−0.22 s.d., 95% CI −0.44 to 0.00; prevalence ratio for stunting: 1.39, 95% CI 0.94–2.06) and potentially lower WAZ. No pathogens were associated with reported diarrhoea in adjusted models. Giardia spp. carriage may be associated with growth faltering, but not diarrhoea, in this and similar low-income settings. Stool-based enteric pathogen detection provides a direct indication of previous exposure that may be useful as a broader endpoint of trials of environmental interventions.
Collapse
|
|
22
|
Dizdar V, Hausken T, Laerum OD, Gilja OH, Langeland N, Hanevik K. Prolonged Duodenal Mucosal Lymphocyte Alterations in Patients With and Without Postinfectious Functional Gastrointestinal Disorders After Giardia Infection. J Infect Dis 2020; 220:321-329. [PMID: 30500895 PMCID: PMC6581897 DOI: 10.1093/infdis/jiy690] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Accepted: 11/28/2018] [Indexed: 12/12/2022] Open
Abstract
Background Persisting low-grade inflammation is suggested to play a role in postinfectious functional gastrointestinal disorders (PI-FGIDs). The present study examined alterations in duodenal mucosal lymphocytes during and after Giardia gastroenteritis in patients who did, or did not, develop PI-FGIDs. Methods Duodenal mucosal intraepithelial lymphocytes (IELs) and lamina propria CD3, CD4, CD8, and CD20 lymphocytes were quantified in 28 patients with chronic giardiasis (CG), 66 patients with persistent abdominal symptoms after acute Giardia infection (PI-FGID), 19 recovered controls (RCs), and 16 healthy volunteers (HCs). Associations with illness duration, abdominal symptoms, and histology grade were assessed. Results Duodenal CD4 IELs were significantly elevated in CG, then decreased, followed by an upward trend after 1 year in both the PI-FGID and RC groups. Duodenal lamina propria crypt CD4 T cells were decreased in CG, and stayed low for about 14 months before normalizing in both the PI-FGID and RC groups. Lamina propria CD20 cells were persistently elevated in all 3 Giardia-exposed groups. Biopsies with microscopic inflammation showed increased lamina propria CD20 levels. Conclusions Duodenal mucosal lymphocyte alterations were prolonged after Giardia infection, but similar in patients who developed PI-FGID and recovered asymptomatic controls.
Collapse
Affiliation(s)
- Vernesa Dizdar
- Department of Medicine, Section of Gastroenterology, Department of Medicine, Bergen, Norway.,National Centre of Functional Gastrointestinal Disorders, Section of Gastroenterology, Department of Medicine, Bergen, Norway
| | - Trygve Hausken
- National Centre of Functional Gastrointestinal Disorders, Section of Gastroenterology, Department of Medicine, Bergen, Norway.,National Centre of Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway
| | - Ole D Laerum
- Gade Laboratory of Pathology, Department of Clinical Research, University of Bergen, Bergen, Norway.,Department of Pathology, Haukeland University Hospital, Bergen, Norway
| | - Odd Helge Gilja
- Department of Medicine, Section of Gastroenterology, Department of Medicine, Bergen, Norway.,National Centre of Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway
| | - Nina Langeland
- Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway.,Haraldsplass Deaconess Hospital, Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - Kurt Hanevik
- Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway.,Norwegian National Advisory Unit on Tropical Infectious Diseases, Department of Medicine, Haukeland University Hospital, Bergen, Norway
| |
Collapse
|
|
23
|
Pogreba-Brown K, Austhof E, Armstrong A, Schaefer K, Zapata LV, McClelland DJ, Batz MB, Kuecken M, Riddle M, Porter CK, Bazaco MC. Chronic Gastrointestinal and Joint-Related Sequelae Associated with Common Foodborne Illnesses: A Scoping Review. Foodborne Pathog Dis 2020; 17:67-86. [PMID: 31589475 PMCID: PMC9246095 DOI: 10.1089/fpd.2019.2692] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
To strengthen the burden estimates for chronic sequelae of foodborne illness, we conducted a scoping review of the current literature for common foodborne pathogens and their associated sequelae. We aim to describe the current literature and gaps in knowledge of chronic sequelae associated with common foodborne illnesses. A comprehensive search was conducted in PubMed, EMBASE, and Web of Science for peer-reviewed articles published January 1, 2000 to April 1, 2018. Articles available in English, of any epidemiological study design, for 10 common foodborne pathogens (Campylobacter, Salmonella, Escherichia coli, Listeria, Shigella, Cryptosporidium, Cyclospora, Giardia, Yersinia, and norovirus) and their associated gastrointestinal (GI)- and joint-related sequelae were included. Of the 6348 titles screened for inclusion, 380 articles underwent full-text review; of those 380, 129 were included for data extraction. Of the bacterial pathogens included in the search terms, the most commonly reported were Salmonella (n = 104) and Campylobacter (n = 99); E. coli (n = 55), Shigella (n = 49), Yersinia (n = 49), and Listeria (n = 15) all had fewer results. Norovirus was the only virus included in our search, with 28 article that reported mostly GI-related sequelae and reactive arthritis (ReA) reported once. For parasitic diseases, Giardia (n = 26) and Cryptosporidium (n = 18) had the most articles, and no results were found for Cyclospora. The most commonly reported GI outcomes were irritable bowel syndrome (IBS; n = 119) and inflammatory bowel disease (n = 29), and ReA (n = 122) or "joint pain" (n = 19) for joint-related sequelae. Salmonella and Campylobacter were most often associated with a variety of outcomes, with ReA (n = 34 and n = 27) and IBS (n = 17 and n = 20) reported most often. This scoping review shows there are still a relatively small number of studies being conducted to understand specific pathogen/outcome relationships. It also shows where important gaps in the impact of chronic sequelae from common foodborne illnesses still exist and where more focused research would best be implemented.
Collapse
Affiliation(s)
- Kristen Pogreba-Brown
- Epidemiology & Biostatistics Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona
| | - Erika Austhof
- Epidemiology & Biostatistics Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona
| | - Alexandra Armstrong
- Epidemiology & Biostatistics Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona
| | - Kenzie Schaefer
- Epidemiology & Biostatistics Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona
| | - Lorenzo Villa Zapata
- Epidemiology & Biostatistics Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona
| | | | | | - Maria Kuecken
- U.S. Food and Drug Administration, College Park, Maryland
| | - Mark Riddle
- Naval Medical Research Center, Silver Spring, Maryland
| | | | | |
Collapse
|
|
24
|
Aykur M, Armagan G, Vardar R, Dagci H. Fecal calprotectin as a factor that supports the pathogenicity of Dientamoeba fragilis. Microb Pathog 2019; 139:103868. [PMID: 31730996 DOI: 10.1016/j.micpath.2019.103868] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 10/21/2019] [Accepted: 11/11/2019] [Indexed: 10/25/2022]
Abstract
Calprotectin is a protein that is mostly released from neutrophils, monocytes, macrophages and submucosal epithelial cells. Fecal calprotectin (f-CP) is a marker of intestinal inflammation. There are some discussions about the pathogenicity of D. fragilis in the gastrointestinal tract. In this study, we investigated whether f-CP level is a factor supporting the pathogenicity of D. fragilis. The f-CP levels were evaluated in patients with only D. fragilis positive in comparison with healthy controls. Moreover, the levels of f-CP were investigated in fecal samples of D. fragilis negative patients with gastrointestinal complaints. The fecal samples were collected from three groups. Three groups of fecal samples were examined directly microscopy, trichrome staining, cultivation, enzyme immunoassay (EIA) and real-time PCR assay. In the first group (Group 1, n = 34), patient stool samples with gastrointestinal symptoms (without other pathogens) found only with D. fragilis were included. In the second group (Group 2, n = 31), there were patients' stool samples with gastrointestinal symptoms that D. fragilis was negative (but there may be other pathogenic agents). In the control group (Group 3, n = 23), we used fecal samples collected from healthy volunteers without any infection or gastrointestinal complaints. The collected fecal samples were stored at -20 °C until analysis. Levels of f-CP were determined by using human calprotectin ELISA kits. Total of 88 patients were enrolled in three different groups. We obtained f-CP levels as follows: 33.40 ng/mg protein in the group 1, 15.99 ng/mg protein in the group 2 and 1.54 ng/mg protein in the group 3. Statistically significant difference in f-CP levels of the group 1 and the group 2 were obtained when compared with healthy controls (p < 0.0001). However, the f-CP levels of the group 1 were not significantly different from the group 2 (p > 0.99). In conclusion, increased levels of f-CP are shown as a marker of an inflammatory disease of the lower gastrointestinal tract in infected humans. There is continues controversy about the pathogenicity of D. fragilis in symptomatic and asymptomatic patients. The findings of this study contribute to the ongoing debate about the pathogenicity of D. fragilis. In our study, the potential pathogenicity of D. fragilis is associated with increased f-CP concentrations with parasite detection in the fecal samples and therefore we assume that the parasite is not only a harmless commensal. In summary, higher levels of f-CP found in D. fragilis positive patients suggest the importance of researches that support the pathogenicity of indicated parasite.
Collapse
Affiliation(s)
- Mehmet Aykur
- Department of Parasitology, Ege University, Faculty of Medicine, Bornova, Izmir, Turkey; Department of Parasitology, Gaziosmanpaşa University, Faculty of Medicine, Tokat, Turkey.
| | - Guliz Armagan
- Department of Biochemistry, Ege University, Faculty of Pharmacy, Bornova, Izmir, Turkey
| | - Rukiye Vardar
- Department of Gastroenterology, Ege University, Faculty of Medicine, Bornova, Izmir, Turkey
| | - Hande Dagci
- Department of Parasitology, Ege University, Faculty of Medicine, Bornova, Izmir, Turkey
| |
Collapse
|
|
25
|
Fontanelli Sulekova L, Gabrielli S, Furzi F, Milardi GL, Biliotti E, De Angelis M, Iaiani G, Fimiani C, Maiorano M, Mattiucci S, Taliani G. Molecular characterization of Blastocystis subtypes in HIV-positive patients and evaluation of risk factors for colonization. BMC Infect Dis 2019; 19:876. [PMID: 31640585 PMCID: PMC6805496 DOI: 10.1186/s12879-019-4537-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Accepted: 10/09/2019] [Indexed: 01/11/2023] Open
Abstract
Background Blastocystis is one of the most common intestinal protozoa in human faecal samples with uncertain impact on public health. Studies on the prevalence of Blastocystis in HIV-positive patients are limited and dated. Methods A cross-sectional study was carried out involving 156 HIV-positive patients to evaluate the prevalence of Blastocystis-subtypes by molecular amplification and sequencing the small subunit rRNA gene (SSU rDNA), to identify the risk factors for its transmission, to examine the relationship between the presence of the protist and gastrointestinal disorders. Furthermore, the evaluation of the faecal calprotectin by immunoassay from a sample of subjects was performed to evaluate the gut inflammation in Blastocystis-carriers. Results Blastocystis-subtypes ST1, ST2, ST3, ST4 were identified in 39 HIV-positive patients (25%). No correlation was found between the presence of the protist and virological or epidemiological risk factors. Blastocystis was more frequently detected in homosexual subjects (p = 0.037) infected by other enteric protozoa (p = 0.0001) and with flatulence (p = 0.024). No significant differences in calprotectin level was found between Blastocystis-carriers and free ones. Conclusions Blastocystis is quite common in HIV-positive patients on ART showing in examined patients 25% prevalence. Homosexual behaviour may represent a risk factor for its transmission, while CD4 count and viremia didn’t correlate with the presence of the protist. The pathogenetic role of Blastocystis remains unclear and no gut inflammation status was detected in Blastocystis-carriers. The only symptom associated with Blastocystis was the flatulence, evidencing a link between the presence of the protist and the composition and stability of gut microbiota.
Collapse
Affiliation(s)
| | - Simona Gabrielli
- Clinical Diagnostic Parasitology laboratory, Umberto I Academic Hospital, 00185, Rome, Italy. .,Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy.
| | - Federica Furzi
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy
| | - Giovanni Luigi Milardi
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy
| | - Elisa Biliotti
- Department of Translation and Precision Medicine, Sapienza University of Rome, 00185, Rome, Italy
| | - Maurizio De Angelis
- Department of Translation and Precision Medicine, Sapienza University of Rome, 00185, Rome, Italy
| | - Giancarlo Iaiani
- Department of Translation and Precision Medicine, Sapienza University of Rome, 00185, Rome, Italy
| | - Caterina Fimiani
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy
| | - Myriam Maiorano
- Department of Translation and Precision Medicine, Sapienza University of Rome, 00185, Rome, Italy
| | - Simonetta Mattiucci
- Clinical Diagnostic Parasitology laboratory, Umberto I Academic Hospital, 00185, Rome, Italy.,Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy
| | - Gloria Taliani
- Department of Translation and Precision Medicine, Sapienza University of Rome, 00185, Rome, Italy
| |
Collapse
|
|
26
|
Burgess SL, Oka A, Liu B, Bolick DT, Oakland DN, Guerrant RL, Bartelt L. Intestinal parasitic infection alters bone marrow derived dendritic cell inflammatory cytokine production in response to bacterial endotoxin in a diet-dependent manner. PLoS Negl Trop Dis 2019; 13:e0007515. [PMID: 31260452 PMCID: PMC6602177 DOI: 10.1371/journal.pntd.0007515] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Accepted: 06/04/2019] [Indexed: 01/09/2023] Open
Abstract
Giardia lamblia is a common intestinal parasitic infection that although often acutely asymptomatic, is associated with debilitating chronic intestinal and extra-intestinal sequelae. In previously healthy adults, a primary sporadic Giardia infection can lead to gut dysfunction and fatigue. These symptoms correlate with markers of inflammation that persist well after the infection is cleared. In contrast, in endemic settings, first exposure occurs in children who are frequently malnourished and also co-infected with other enteropathogens. In these children, Giardia rarely causes symptoms and associates with several decreased markers of inflammation. Mechanisms underlying these disparate and potentially enduring outcomes following Giardia infection are not presently well understood. A body of work suggests that the outcome of experimental Giardia infection is influenced by the nutritional status of the host. Here, we explore the consequences of experimental Giardia infection under conditions of protein sufficiency or deficiency on cytokine responses of ex vivo bone marrow derived dendritic cells (BMDCs) to endotoxin stimulation. We show that BMDCs from Giardia- challenged mice on a protein sufficient diet produce more IL-23 when compared to uninfected controls whereas BMDCs from Giardia challenged mice fed a protein deficient diet do not. Further, in vivo co-infection with Giardia attenuates robust IL-23 responses in endotoxin-stimulated BMDCs from protein deficient mice harboring enteroaggregative Escherichia coli. These results suggest that intestinal Giardia infection may have extra-intestinal effects on BMDC inflammatory cytokine production in a diet dependent manner, and that Giardia may influence the severity of the innate immune response to other enteropathogens. This work supports recent findings that intestinal microbial exposure may have lasting influences on systemic inflammatory responses, and may provide better understanding of potential mechanisms of post-infectious sequelae and clinical variation during Giardia and enteropathogen co-infection.
Collapse
Affiliation(s)
- Stacey L. Burgess
- Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia, United States of America
| | - Akihiko Oka
- Center for Gastrointestinal Biology and Disease and the Departments of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
| | - Bo Liu
- Division of Infectious Diseases, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America
| | - David T. Bolick
- Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia, United States of America
| | - David Noah Oakland
- Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia, United States of America
| | - Richard L. Guerrant
- Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia, United States of America
| | - Luther Bartelt
- Center for Gastrointestinal Biology and Disease and the Departments of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
- Division of Infectious Diseases, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America
| |
Collapse
|
|
27
|
Meningher T, Boleslavsky D, Barshack I, Tabibian-Keissar H, Kohen R, Gur-Wahnon D, Ben-Dov IZ, Sidi Y, Avni D, Schwartz E. Giardia lamblia miRNAs as a new diagnostic tool for human giardiasis. PLoS Negl Trop Dis 2019; 13:e0007398. [PMID: 31206518 PMCID: PMC6597124 DOI: 10.1371/journal.pntd.0007398] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 06/27/2019] [Accepted: 04/16/2019] [Indexed: 01/15/2023] Open
Abstract
Background Giardia lamblia is a very common cause of gastrointestinal symptoms worldwide. There are several methods for the diagnosis of Giardia infection, however none are ideal. We aim to find a new, microRNA-based method that will improve the currently available diagnostic methods for giardiasis. Methods Deep-sequence profiling of Giardia small-RNA revealed that miR5 and miR6 are highly expressed in Giardia. These miRNAs were tested by qRT-PCR in duodenal biopsies of patients with giardiasis who were positive by microscopic pathological evaluation. The gastric biopsies of the same patients served as negative control tissues. Additionally, these miRNAs were evaluated in stool samples of patients with proven giardiasis. Results All histologically proven duodenal biopsies of patients with Giardia infection were positive for Giardia miR5, with a mean threshold cycle (Ct) of 23.7, as well as for Giardia DNA qPCR (16S-like gene, mean Ct 26.3). Gastric biopsies which were tested as a control all were negative. Stool evaluation of miR6 in patients with giardiasis showed 90% specificity but only 66% sensitivity, and a lower accuracy rate was obtained with miR5. Conclusion Giardia miR5 testing in duodenal biopsies may be a new method for the diagnosis of giardiasis. It seems to be more sensitive when compared with testing for Giardia DNA by qPCR in duodenal biopsies. It will be important to investigate the contribution of routine Giardia miRNA testing in duodenal biopsies from patients with persistent abdominal symptoms Giardiasis is a major cause of diarrheal disease throughout the world. It is more common in areas with poor sanitation such as in many low-income countries, but it occurs in high-income countries as well. It is the most commonly identified intestinal parasite in the United States and it is endemic in other industrialized countries. The causative agent is the flagellate protozoan Giardia lamblia, and transmission is mainly by the fecal-oral route. The basic method of diagnosis is stool examination. It is usually found through stool microscopy examination which should be performed on fresh stool and repeated in 3 days. Despite some newer diagnostic methods, Giardia is still difficult to detect, often leading to misdiagnoses. In this study we show that using Giardia microRNA (miR5) as a marker for Giardia infection in duodenal biopsies may be a new method for diagnosis of giardiasis. It appears to be more sensitive than histological diagnosis and also more sensitive than Giardia DNA testing in duodenal biopsies. Interestingly, in our patients, duodenal biopsies were done for persistent abdominal symptoms and the finding of Giardia in their biopsy was unexpected. Thus, testing duodenal biopsies for Giardia miRNA in patients with persistent abdominal symptoms might contribute to diagnosis and prompt treatment for those with giardiasis.
Collapse
Affiliation(s)
- Tal Meningher
- Laboratory of Molecular Cell Biology, Sheba Medical Center, Ramat Gan, Israel
- Department of Medicine C, Sheba Medical Center, Ramat Gan, Israel
- Molecular Laboratory for the Study of Tropical Diseases, Sheba Medical Center, Ramat Gan, Israel
| | | | - Iris Barshack
- Department of Pathology, Sheba Medical Center, Ramat Gan, Israel
- Faculty of Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Hila Tabibian-Keissar
- Department of Pathology, Sheba Medical Center, Ramat Gan, Israel
- The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
| | - Refael Kohen
- Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel
| | - Devorah Gur-Wahnon
- Laboratory of Medical Transcriptomics, Nephrology and Hypertension Services, Hadassah—Hebrew University Medical Center, Jerusalem, Israel
| | - Iddo Z. Ben-Dov
- Laboratory of Medical Transcriptomics, Nephrology and Hypertension Services, Hadassah—Hebrew University Medical Center, Jerusalem, Israel
| | - Yechezkel Sidi
- Laboratory of Molecular Cell Biology, Sheba Medical Center, Ramat Gan, Israel
- Department of Medicine C, Sheba Medical Center, Ramat Gan, Israel
- Faculty of Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Dror Avni
- Laboratory of Molecular Cell Biology, Sheba Medical Center, Ramat Gan, Israel
- Department of Medicine C, Sheba Medical Center, Ramat Gan, Israel
- Molecular Laboratory for the Study of Tropical Diseases, Sheba Medical Center, Ramat Gan, Israel
- * E-mail: , (DA); (ES)
| | - Eli Schwartz
- Molecular Laboratory for the Study of Tropical Diseases, Sheba Medical Center, Ramat Gan, Israel
- Faculty of Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
- The Center for Geographic Medicine, Sheba Medical Center, Ramat Gan, Israel
- * E-mail: , (DA); (ES)
| |
Collapse
|
|
28
|
Identification of Conserved Candidate Vaccine Antigens in the Surface Proteome of Giardia lamblia. Infect Immun 2019; 87:IAI.00219-19. [PMID: 30962402 DOI: 10.1128/iai.00219-19] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Accepted: 04/01/2019] [Indexed: 01/08/2023] Open
Abstract
Giardia lamblia, one of the most common protozoal infections of the human intestine, is an important worldwide cause of diarrheal disease, malabsorption, malnutrition, delayed cognitive development in children, and protracted postinfectious syndromes. Despite its medical importance, no human vaccine is available against giardiasis. A crude veterinary vaccine has been developed, and experimental vaccines based on expression of multiple variant-specific surface proteins have been reported, but poorly defined vaccine components and excessive antigen variability are problematic for pharmaceutical vaccine production. To expand the repertoire of antigen candidates for vaccines, we reasoned that surface proteins may provide an enriched source of such antigens since key host effectors, such as secretory IgA, can directly bind to such antigens in the intestinal lumen and interfere with epithelial attachment. Here, we have applied a proteomics approach to identify 23 novel surface antigens of G. lamblia that show >90% amino acid sequence identity between the two human-pathogenic genetic assemblages (A and B) of the parasite. Surface localization of a representative subset of these proteins was confirmed by immunostaining. Four selected proteins, uridine phosphorylase-like protein-1, protein 21.1 (GL50803_27925), α1-giardin, and α11-giardin, were subsequently produced in recombinant form and shown to be immunogenic in mice and G. lamblia-infected humans and confer protection against G. lamblia infection upon intranasal immunization in rodent models of giardiasis. These results demonstrate that identification of conserved surface antigens provides a powerful approach for overcoming a key rate-limiting step in the design and construction of an effective vaccine against giardiasis.
Collapse
|
|
29
|
Hanevik K, Wik E, Langeland N, Hausken T. Transient elevation of anti-transglutaminase and anti-endomysium antibodies in Giardia infection. Scand J Gastroenterol 2018; 53:809-812. [PMID: 29911457 DOI: 10.1080/00365521.2018.1481522] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Markers of celiac disease (CeD) may be elevated in various conditions of intestinal inflammation or autoimmune disease. Recent reports argue that intestinal infection may induce development of CeD in susceptible individuals. Serum anti-tissue transglutaminase (tTG) and anti-endomysium antibodies (EMA) have been proposed in previous reports to be helpful in differentiating between giardiasis and CeD. In this report, we describe eight cases with elevated CeD serological markers and pathological duodenal histology during, or shortly after, Giardia infection. We present follow-up clinical and serological findings to determine which of these that were diagnosed with CeD. Serum levels of tTGand EMA did not discriminate well between patients where CeD was excluded, and those who were later diagnosed with CeD. The value of these serological CeD markers is discussed in relation to CeD diagnosis in cases with chronic or recent giardiasis.
Collapse
Affiliation(s)
- Kurt Hanevik
- a Department of Clinical Science , University of Bergen , Bergen , Norway.,b National Advisory Center for Tropical Infectious Diseases, Department of Medicine , Haukeland University Hospital , Bergen , Norway
| | - Elisabeth Wik
- c Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine , University of Bergen , Bergen , Norway.,d Department of Pathology , Haukeland University Hospital , Bergen , Norway
| | - Nina Langeland
- a Department of Clinical Science , University of Bergen , Bergen , Norway.,b National Advisory Center for Tropical Infectious Diseases, Department of Medicine , Haukeland University Hospital , Bergen , Norway
| | - Trygve Hausken
- e National Centre of Functional Gastrointestinal Disorders, Section of Gastroenterology, Department of Medicine , Haukeland University Hospital , Bergen , Norway
| |
Collapse
|
|
30
|
Kumar S, Bains T, Won Kim AS, Tam C, Kim J, Cheng LW, Land KM, Debnath A, Kumar V. Highly Potent 1 H-1,2,3-Triazole-Tethered Isatin-Metronidazole Conjugates Against Anaerobic Foodborne, Waterborne, and Sexually-Transmitted Protozoal Parasites. Front Cell Infect Microbiol 2018; 8:380. [PMID: 30425970 PMCID: PMC6218680 DOI: 10.3389/fcimb.2018.00380] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2018] [Accepted: 10/09/2018] [Indexed: 12/26/2022] Open
Abstract
Parasitic infections like amebiasis, trichomoniasis, and giardiasis are major health threats in tropical and subtropical regions of the world. Metronidazole (MTZ) is the current drug of choice for amebiasis, giardiasis, and trichomoniasis but it has several adverse effects and potential resistance is a concern. In order to develop alternative antimicrobials, a library of 1H-1,2,3-triazole-tethered metronidazole-isatin conjugates was synthesized using Huisgen's azide-alkyne cycloaddition reaction and evaluated for their amebicidal, anti-trichomonal, and anti-giardial potential. Most of the synthesized conjugates exhibited activities against Trichomonas vaginalis, Tritrichomonas foetus, Entamoeba histolytica, and Giardia lamblia. While activities against T. vaginalis and T. foetus were comparable to that of the standard drug MTZ, better activities were observed against E. histolytica and G. lamblia. Conjugates 9d and 10a were found to be 2–3-folds more potent than MTZ against E. histolytica and 8–16-folds more potent than MTZ against G. lamblia. Further analysis of these compounds on fungi and bacteria did not show inhibitory activity, demonstrating their specific anti-protozoal properties.
Collapse
Affiliation(s)
- Sumit Kumar
- Department of Chemistry, Guru Nanak Dev University, Amritsar, India
| | - Trpta Bains
- Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, United States
| | - Ashley Sae Won Kim
- Department of Biological Sciences, University of the Pacific, Stockton, CA, United States
| | - Christina Tam
- Foodborne Toxin Detection and Prevention Research Unit, Agricultural Research Service, United States Department of Agriculture, Albany, CA, United States
| | - Jong Kim
- Foodborne Toxin Detection and Prevention Research Unit, Agricultural Research Service, United States Department of Agriculture, Albany, CA, United States
| | - Luisa W Cheng
- Foodborne Toxin Detection and Prevention Research Unit, Agricultural Research Service, United States Department of Agriculture, Albany, CA, United States
| | - Kirkwood M Land
- Department of Biological Sciences, University of the Pacific, Stockton, CA, United States
| | - Anjan Debnath
- Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, United States
| | - Vipan Kumar
- Department of Chemistry, Guru Nanak Dev University, Amritsar, India
| |
Collapse
|
|
31
|
Jha AK, Chaudhary M, Dayal VM, Kumar A, Jha SK, Jha P, Purkayastha S, Ranjan R. Optimal cut-off value of fecal calprotectin for the evaluation of ulcerative colitis: An unsolved issue? JGH OPEN 2018; 2:207-213. [PMID: 30483591 PMCID: PMC6207035 DOI: 10.1002/jgh3.12074] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Revised: 06/10/2018] [Accepted: 06/23/2018] [Indexed: 12/12/2022]
Abstract
Introduction There is variability in the fecal calprotectin (FCP) cut‐off level for the prediction of ulcerative colitis (UC) disease activity and differentiation from irritable bowel disease (IBS‐D). The FCP cut‐off levels vary from country to country. Aims We aimed to assess FCP as a marker of disease activity in patients with UC. We determined the optimal FCP cut‐off value for differentiating UC and IBS‐D. Methods In a prospective study, we enrolled 76 UC and 30 IBS‐D patients. We studied the correlation of FCP with disease activity/extent as well as its role in differentiating UC from IBS‐D. We also reviewed literature regarding the optimal FCP cut‐off level for the prediction of disease activity and differentiation from IBS‐D patients. Results Sensitivity, specificity, positive predictive value, and negative predictive value of FCP (cut‐off level, 158 μg/g) for the prediction of complete mucosal healing (using Mayo endoscopic subscore) were 90, 85, 94.7, and 73.3%, respectively. Sensitivity, specificity, positive predictive value, and negative predictive value of FCP (cut‐off level, 425 μg/g) for the prediction of inactive disease (Mayo Score ≤ 2) were 94.3, 88.7, 86.2, and 95.4%, respectively. We also found a FCP cut‐off value of 188 μg/g for the differentiation of UC from IBS‐D. Conclusions The study reveals the large quantitative differences in FCP cut‐off levels in different study populations. This study demonstrates a wide variation in FCP cut‐off levels in the initial diagnosis of UC as well as in follow‐up post‐treatment. Therefore, this test requires validation of the available test kits and finding of appropriate cut‐off levels for different study populations.
Collapse
Affiliation(s)
- Ashish Kumar Jha
- Department of Gastroenterology Indira Gandhi Institute of Medical Sciences Patna India
| | - Madhur Chaudhary
- Department of Gastroenterology Indira Gandhi Institute of Medical Sciences Patna India
| | - Vishwa Mohan Dayal
- Department of Gastroenterology Indira Gandhi Institute of Medical Sciences Patna India
| | - Amarendra Kumar
- Department of Gastroenterology Indira Gandhi Institute of Medical Sciences Patna India
| | - Sanjeev Kumar Jha
- Department of Gastroenterology Indira Gandhi Institute of Medical Sciences Patna India
| | - Praveen Jha
- Department of Gastroenterology Indira Gandhi Institute of Medical Sciences Patna India
| | - Shubham Purkayastha
- Department of Gastroenterology Indira Gandhi Institute of Medical Sciences Patna India
| | - Ravish Ranjan
- Department of Gastroenterology Indira Gandhi Institute of Medical Sciences Patna India
| |
Collapse
|
|
32
|
Ma'ayeh SY, Knörr L, Sköld K, Garnham A, Ansell BRE, Jex AR, Svärd SG. Responses of the Differentiated Intestinal Epithelial Cell Line Caco-2 to Infection With the Giardia intestinalis GS Isolate. Front Cell Infect Microbiol 2018; 8:244. [PMID: 30062089 PMCID: PMC6055019 DOI: 10.3389/fcimb.2018.00244] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Accepted: 06/25/2018] [Indexed: 12/11/2022] Open
Abstract
Giardia intestinalis is a parasitic protist that causes diarrhea in humans, affecting mainly children of the developing world, elderly and immunocompromised individuals. Humans are infected by two major Giardia assemblages (i.e. genetic subtypes), A and B, with the latter being the most common. So far, there is little information on molecular or cellular changes during infections with assemblage B. Here, we used RNA sequencing to study transcriptional changes in Caco-2 intestinal epithelial cells (IECs) co-incubated with assemblage B (GS isolate) trophozoites for 1.5, 3, and 4.5 h. We aimed to identify early molecular events associated with the establishment of infection and followed cellular protein changes up to 10 h. IEC transcriptomes showed a dominance of immediate early response genes which was sustained across all time points. Transcription of inflammatory cytokines (e.g., cxcl1-3, ccl2, 1l1a, and il1b) peaked at 1.5 and 3 h of infection. Compared to co-incubation with assemblage A Giardia, we identified the induction of novel cytokines (cxcl8, cxcl10, csf1, cx3cl1, il12a, il11) and showed that inflammatory signaling is mediated by Erk1/2 phosphorylation (mitogen activated protein kinase, MAPK), nuclear factor kappa B (NFκB) and adaptor protein-1 (AP-1). We also showed that GS trophozoites attenuate P38 (MAPK) phosphorylation in IECs. Low amounts of IL-8, CXCL1 and CCL20 proteins were measured in the interaction medium, which was attributed to cytokine degradation by trophozoite secreted proteases. Based on the transcriptome, the decay of cytokines mRNA mediated by zinc finger protein 36 might be another mechanism controlling cytokine levels at later time points. IEC transcriptomes suggested homeostatic responses to counter oxidative stress, glucose starvation, and disturbances in amino acid and lipid metabolism. A large group of differentially transcribed genes were associated with cell cycle arrest and induction of apoptosis, which was validated at protein level. IEC transcriptomes also suggested changes in tight junction's integrity, microvilli structure and the extracellular mucin layer. This is the first study to illuminate transcriptional and protein regulatory events underlying IECs responses and pathogenesis during Giardia assemblage B infection. It highlights differences compared to assemblage A infections which might account for the differences observed in human infections with the two assemblages.
Collapse
Affiliation(s)
- Showgy Y Ma'ayeh
- Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden
| | - Livia Knörr
- Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden
| | - Karin Sköld
- Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden
| | - Alexandra Garnham
- Population Health & Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
| | - Brendan R E Ansell
- Population Health & Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.,Faculty of Veterinary Science, The University of Melbourne, Parkville, VIC, Australia
| | - Aaron R Jex
- Population Health & Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.,Faculty of Veterinary Science, The University of Melbourne, Parkville, VIC, Australia
| | - Staffan G Svärd
- Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden
| |
Collapse
|
|
33
|
Dann SM, Le CHY, Hanson EM, Ross MC, Eckmann L. Giardia Infection of the Small Intestine Induces Chronic Colitis in Genetically Susceptible Hosts. THE JOURNAL OF IMMUNOLOGY 2018; 201:548-559. [PMID: 29898958 DOI: 10.4049/jimmunol.1700824] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Accepted: 05/07/2018] [Indexed: 01/01/2023]
Abstract
The lumen-dwelling protozoan Giardia is an important parasitic cause of diarrheal disease worldwide. Infection can persist over extended periods with minimal intestinal inflammation, suggesting that Giardia may attenuate host responses to ensure its survival, although clearance eventually occurs in most cases. IL-10 is an anti-inflammatory regulator critical for intestinal homeostasis and controlling host responses to bacterial exposure, yet its potential role in coordinating antiprotozoal host defense in the intestine is not known. In this study, we found that murine infection with the natural enteric pathogen Giardia muris induced a transient IL-10 response after 2-4 wk at the primary site of infection in the upper small intestine, but parasite colonization and eradication were not affected by the absence of the cytokine in gene-targeted mice. However, IL-10 was critical for controlling infection-associated immunological sequelae in the colon because severe and persistent diarrhea and colitis were observed in IL-10-deficient mice within 1-2 wk postinfection but not in uninfected littermate controls. Inflammation was characterized by epithelial hyperplasia, neutrophil and macrophage expansion, and Th1 induction and could be prevented by blockade of IL-12/IL-23 p40 but not depletion of CD11c+ dendritic cells. Furthermore, the intestinal microbiota underwent characteristic shifts in composition and was required for disease because antibiotics and loss of TLR signaling in MyD88-deficient mice protected against colitis. Together, our data suggest that transient infection by a luminal and seemingly noninflammatory pathogen can trigger sustained colitis in genetically susceptible hosts, which has broader implications for understanding postinfectious syndromes and other chronic intestinal inflammatory conditions.
Collapse
Affiliation(s)
- Sara M Dann
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555.,Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555
| | - Christine H Y Le
- Department of Medicine, University of California, San Diego, La Jolla, CA 92093; and
| | - Elaine M Hanson
- Department of Medicine, University of California, San Diego, La Jolla, CA 92093; and
| | - Matthew C Ross
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030
| | - Lars Eckmann
- Department of Medicine, University of California, San Diego, La Jolla, CA 92093; and
| |
Collapse
|
|
34
|
Pecková R, Sak B, Květoňová D, Kváč M, Koriťáková E, Foitová I. The course of experimental giardiasis in Mongolian gerbil. Parasitol Res 2018; 117:2437-2443. [PMID: 29797082 DOI: 10.1007/s00436-018-5932-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Accepted: 05/15/2018] [Indexed: 11/26/2022]
Abstract
Fifteen Mongolian gerbils were inoculated with 10 × 106 viable trophozoites of Giardia intestinalis. Their faeces were examined daily by flotation method and the number of shed cysts was counted. Two animals (male and female) were euthanised at 4- to 5-day intervals (9, 14, 18 days post-infection (DPI)). The remaining nine gerbils were sacrificed and dissected at the end of the experiment (23 DPI). Their small intestinal tissues were processed for examination using histological sectioning and scanning electron microscopy and their complete blood count (CBC) was examined. The highest number of trophozoites at the total was observed in the duodenum in gerbils sacrificed on 14 DPI. Number of shed cysts was positively correlated with number of trophozoites rinsed from the intestine. Infected gerbils had lower body weight gain in comparison with control group and in three male gerbils; diarrhoea occurred during infection. Cyst shedding was negatively correlated with values of mean corpuscular haemoglobin concentration. Females showed another pattern in cyst shedding than males. This information needs to be taken into account while planning the experiments.
Collapse
Affiliation(s)
- Radka Pecková
- Department of Botany and Zoology, Faculty of Science, Masaryk University, Kotlářská 2, 611 37, Brno, Czech Republic.
| | - Bohumil Sak
- Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, v.v.i., Branišovská 31, 37005, České Budějovice, Czech Republic
| | - Dana Květoňová
- Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, v.v.i., Branišovská 31, 37005, České Budějovice, Czech Republic
| | - Martin Kváč
- Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, v.v.i., Branišovská 31, 37005, České Budějovice, Czech Republic
| | - Eva Koriťáková
- Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Ivona Foitová
- Department of Botany and Zoology, Faculty of Science, Masaryk University, Kotlářská 2, 611 37, Brno, Czech Republic
| |
Collapse
|
|
35
|
Cacciò SM, Lalle M, Svärd SG. Host specificity in the Giardia duodenalis species complex. INFECTION GENETICS AND EVOLUTION 2017; 66:335-345. [PMID: 29225147 DOI: 10.1016/j.meegid.2017.12.001] [Citation(s) in RCA: 133] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Revised: 12/01/2017] [Accepted: 12/02/2017] [Indexed: 12/15/2022]
Abstract
Giardia duodenalis is a unicellular flagellated parasite that infects the gastrointestinal tract of a wide range of mammalian species, including humans. Investigations of protein and DNA polymorphisms revealed that G. duodenalis should be considered as a species complex, whose members, despite being morphologically indistinguishable, can be classified into eight groups, or Assemblages, separated by large genetic distances. Assemblages display various degree of host specificity, with Assemblages A and B occurring in humans and many other hosts, Assemblage C and D in canids, Assemblage E in hoofed animals, Assemblage F in cats, Assemblage G in rodents, and Assemblage H in pinnipeds. The factors determining host specificity are only partially understood, and clearly involve both the host and the parasite. Here, we review the results of in vitro and in vivo experiments, and clinical observations to highlight relevant biological and genetic differences between Assemblages, with a focus on human infection.
Collapse
Affiliation(s)
- Simone M Cacciò
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy.
| | - Marco Lalle
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Staffan G Svärd
- Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden
| |
Collapse
|
|
36
|
Abstract
PURPOSE OF REVIEW Giardia is a common intestinal parasite worldwide, and infection can be associated with clear and sometimes persistent symptomatology. However, in children in high-prevalence settings, it is not associated with or is perhaps even protective against acute diarrhea, and the association with long-term outcomes has been difficult to discern. RECENT FINDINGS Recent studies have made progress in helping us disentangle this apparent paradox. First, prospective, well-characterized cohort studies have added to the data on the association between Giardia and diarrhea in these settings and have further characterized associations between Giardia infection and nutrition, gut function, and growth. Second, animal models have further characterized the host response to Giardia and helped elucidate mechanisms by which Giardia could impair child development. Finally, new work has shed light on the heterogeneity of human Giardia strains, which may both explain discrepant findings in the literature and help guide higher-resolution analyses of this pathogen in the future. SUMMARY The true clinical impact of endemic pediatric giardiasis remains unclear, but recent prospective studies have confirmed a high prevalence of persistent, subclinical Giardia infections and associated growth shortfalls. Integrating how nutritional, microbial, metabolic, and pathogen-strain variables influence these outcomes could sharpen delineations between pathogenic and potentially beneficial attributes of this enigmatic parasite.
Collapse
|
|
37
|
Galli G, Purchiaroni F, Lahner E, Sacchi MC, Pilozzi E, Corleto VD, Di Giulio E, Annibale B. Time trend occurrence of duodenal intraepithelial lymphocytosis and celiac disease in an open access endoscopic population. United European Gastroenterol J 2017; 5:811-818. [PMID: 29026595 PMCID: PMC5625866 DOI: 10.1177/2050640616680971] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Accepted: 10/30/2016] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Duodenal intraepithelial lymphocytosis (DIL) is a histological finding characterized by the increase of intraepithelial CD3T-lymphocytes over the normal value without villous atrophy, mostly associated to coeliac disease (CD), Helicobacter pylori (Hp) gastritis and autoimmune diseases. OBJECTIVE To assess the occurrence of DIL, CD and Hp gastritis in an endoscopic population over a 13 year period. METHODS From 2003 to 2015 we included adult patients who consecutively underwent oesophago-gastro-duodenoscopy (OGD) with duodenal biopsies assessing the overall and annual occurrence of DIL and CD and the prevalence of Hp gastritis. RESULTS 160 (2.3%) patients with DIL and 275 (3.9%) with CD were detected among 7001 patients. CD occurrence was higher from 2003 to 2011, while since 2012 DIL occurrence gradually increased significantly compared to CD (p = 0.03). DIL patients were more frequently female (p = 0.0006) and underwent OGD more frequently for dyspepsia (p = 0.002) and for indications not related to gastrointestinal symptoms than CD patients (p = 0.0003). Hp gastritis occurred similarly in CD and DIL patients but the latter had higher frequency of atrophic body gastritis (p = 0.005). CONCLUSIONS DIL is a condition increasing in the general endoscopic population mainly diagnosed by chance. Concomitant gastric histological evaluation is able in one third of DIL patients to identify associated possible causes of DIL, such as Hp and atrophic gastritis.
Collapse
Affiliation(s)
- Gloria Galli
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant’Andrea Hospital, School of Medicine, University Sapienza, Rome, Italy
| | - Flaminia Purchiaroni
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant’Andrea Hospital, School of Medicine, University Sapienza, Rome, Italy
| | - Edith Lahner
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant’Andrea Hospital, School of Medicine, University Sapienza, Rome, Italy
| | - Maria Carlotta Sacchi
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant’Andrea Hospital, School of Medicine, University Sapienza, Rome, Italy
| | - Emanuela Pilozzi
- Clinical Molecular Medicine Department, Sant’Andrea Hospital, School of Medicine, University Sapienza, Rome, Italy
| | - Vito Domenico Corleto
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant’Andrea Hospital, School of Medicine, University Sapienza, Rome, Italy
| | - Emilio Di Giulio
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant’Andrea Hospital, School of Medicine, University Sapienza, Rome, Italy
| | - Bruno Annibale
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant’Andrea Hospital, School of Medicine, University Sapienza, Rome, Italy
- Bruno Annibale, Dipartimento Medico-Chirurgico e Medicina Traslazionale, University Sapienza, Sant’Andrea Hospital, Via di Grottarossa 1035, 00189 Rome, Italy.
| |
Collapse
|
|
38
|
Zambrano LD, Priest JW, Ivan E, Rusine J, Nagel C, Kirby M, Rosa G, Clasen TF. Use of Serologic Responses against Enteropathogens to Assess the Impact of a Point-of-Use Water Filter: A Randomized Controlled Trial in Western Province, Rwanda. Am J Trop Med Hyg 2017; 97:876-887. [PMID: 28749764 PMCID: PMC5590594 DOI: 10.4269/ajtmh.16-1006] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Accepted: 05/29/2017] [Indexed: 12/28/2022] Open
Abstract
Diarrhea is a leading contributor to childhood morbidity and mortality in sub-Saharan Africa. Given the challenge of blinding most water, sanitation, and hygiene (WASH) interventions, diarrheal disease outcome measures in WASH intervention trials are subject to potential bias and misclassification. Using the platform of a cluster-randomized controlled trial of a household-based drinking water filter in western province, Rwanda, we assessed the impact of the drinking water filter on enteric seroconversion in young children as a health outcome and examined the association between serologic responses and caregiver-reported diarrhea. Among the 2,179 children enrolled in the trial, 189 children 6-12 months of age were enrolled in a nested serology study. These children had their blood drawn at baseline and 6-12 months after the intervention was distributed. Multiplex serologic assays for Giardia, Cryptosporidium, Entamoeba histolytica, norovirus, Campylobacter, enterotoxigenic Escherichia coli and Vibrio cholerae were performed. Despite imperfect uptake, receipt of the water filter was associated with a significant decrease in seroprevalence of IgG directed against Cryptosporidium parvum Cp17 and Cp23 (relative risk [RR]: 0.62, 95% confidence interval [CI]: 0.44-0.89). Serologic responses were positively associated with reported diarrhea in the previous 7 days for both Giardia intestinalis (RR: 1.94, 95% CI: 1.04-3.63) and C. parvum (RR: 2.21, 95% CI: 1.09-4.50). Serologic responses for all antigens generally increased in the follow-up round, rising sharply after 12 months of age. The water filter is associated with reduced serologic responses against C. parvum, a proxy for exposure and infection; therefore, serologic responses against protozoa may be a suitable health outcome measure for WASH trials among children with diarrhea.
Collapse
Affiliation(s)
- Laura Divens Zambrano
- Department of Environmental Health, Emory University Rollins School of Public Health, Atlanta, Georgia
| | - Jeffrey W. Priest
- Division of Foodborne, Waterborne and Environmental Diseases, National Center for Zoonotic and Emerging Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Emil Ivan
- National Reference Laboratory, Rwanda Biomedical Center, Kigali, Rwanda
| | - John Rusine
- National Reference Laboratory, Rwanda Biomedical Center, Kigali, Rwanda
| | - Corey Nagel
- OHSU/PSU School of Public Health, Oregon Health and Science University, Portland, Oregon
| | - Miles Kirby
- Department of Disease Control, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Ghislaine Rosa
- Department of Disease Control, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Thomas F. Clasen
- Department of Environmental Health, Emory University Rollins School of Public Health, Atlanta, Georgia
- Department of Disease Control, London School of Hygiene and Tropical Medicine, London, United Kingdom
| |
Collapse
|
|
39
|
Rogawski ET, Bartelt LA, Platts-Mills JA, Seidman JC, Samie A, Havt A, Babji S, Trigoso DR, Qureshi S, Shakoor S, Haque R, Mduma E, Bajracharya S, Gaffar SMA, Lima AAM, Kang G, Kosek MN, Ahmed T, Svensen E, Mason C, Bhutta ZA, Lang DR, Gottlieb M, Guerrant RL, Houpt ER, Bessong PO. Determinants and Impact of Giardia Infection in the First 2 Years of Life in the MAL-ED Birth Cohort. J Pediatric Infect Dis Soc 2017; 6:153-160. [PMID: 28204556 PMCID: PMC5907871 DOI: 10.1093/jpids/piw082] [Citation(s) in RCA: 104] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Accepted: 11/28/2016] [Indexed: 11/13/2022]
Abstract
BACKGROUND. Giardia are among the most common enteropathogens detected in children in low-resource settings. We describe here the epidemiology of infection with Giardia in the first 2 years of life in the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED), a multisite birth-cohort study. METHODS. From 2089 children, 34916 stool samples collected during monthly surveillance and episodes of diarrhea were tested for Giardia using an enzyme immunoassay. We quantified the risk of Giardia detection, identified risk factors, and assessed the associations with micronutrients, markers of gut inflammation and permeability, diarrhea, and growth using multivariable linear regression. RESULTS. The incidence of at least 1 Giardia detection varied according to site (range, 37.7%-96.4%) and was higher in the second year of life. Exclusive breastfeeding (HR for first Giardia detection in a monthly surveillance stool sample, 0.46 [95% confidence interval (CI), 0.28-0.75]), higher socioeconomic status (HR, 0.74 [95% CI, 0.56-0.97]), and recent metronidazole treatment (risk ratio for any surveillance stool detection, 0.69 [95% CI, 0.56-0.84]) were protective. Persistence of Giardia (consecutive detections) in the first 6 months of life was associated with reduced subsequent diarrheal rates in Naushahro Feroze, Pakistan but not at any other site. Giardia detection was also associated with an increased lactulose/mannitol ratio. Persistence of Giardia before 6 months of age was associated with a -0.29 (95% CI, -0.53 to -0.05) deficit in weight-for-age z score and -0.29 (95% CI, -0.64 to 0.07) deficit in length-for-age z score at 2 years. CONCLUSIONS. Infection with Giardia occurred across epidemiological contexts, and repeated detections in 40% of the children suggest that persistent infections were common. Early persistent infection with Giardia, independent of diarrhea, might contribute to intestinal permeability and stunted growth.
Collapse
Affiliation(s)
- Elizabeth T. Rogawski
- Division of Infectious Diseases and International Health, University of Virginia, Charlottesville
| | - Luther A. Bartelt
- Division of Infectious Diseases, University of North Carolina-Chapel Hill
| | - James A. Platts-Mills
- Division of Infectious Diseases and International Health, University of Virginia, Charlottesville
| | - Jessica C. Seidman
- Fogarty International Center, National Institutes of Health, Bethesda, Maryland
| | | | - Alexandre Havt
- Clinical Research Unit and Institute of Biomedicine, Federal University of Ceara, Fortaleza, Brazil
| | | | | | | | | | - Rashidul Haque
- International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh
| | | | | | | | - Aldo A. M. Lima
- Clinical Research Unit and Institute of Biomedicine, Federal University of Ceara, Fortaleza, Brazil
| | | | - Margaret N. Kosek
- Asociación Benéfica PRISMA, Iquitos, Peru;,Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
| | - Tahmeed Ahmed
- International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh
| | | | - Carl Mason
- Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; and
| | | | - Dennis R. Lang
- Foundation for the National Institutes of Health, Bethesda, Maryland
| | - Michael Gottlieb
- Foundation for the National Institutes of Health, Bethesda, Maryland
| | - Richard L. Guerrant
- Division of Infectious Diseases and International Health, University of Virginia, Charlottesville
| | - Eric R. Houpt
- Division of Infectious Diseases and International Health, University of Virginia, Charlottesville
| | | | | |
Collapse
|
|
40
|
Garzón M, Pereira-da-Silva L, Seixas J, Papoila AL, Alves M, Ferreira F, Reis A. Association of enteric parasitic infections with intestinal inflammation and permeability in asymptomatic infants of São Tomé Island. Pathog Glob Health 2017; 111:116-127. [PMID: 28279129 PMCID: PMC5445637 DOI: 10.1080/20477724.2017.1299831] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
The cumulative effect of repeated asymptomatic enteric infections on intestinal barrier is not fully understood in infants. We aimed to evaluate the association between previous enteric parasitic infections and intestinal inflammation and permeability at 24-months of age, in asymptomatic infants of São Tomé Island. A subset of infants from a birth cohort, with intestinal parasite evaluations in at least four points of assessment, was eligible. Intestinal inflammatory response and permeability were assessed using fecal S100A12 and alpha-1-antitrypsin (A1AT), respectively. The cutoff <-1SD for weight-for-length and length-for-age was used to define wasting and stunting. Multivariable linear regression analysis explored if cumulative enteric parasitic infections explained variability of fecal biomarkers, after adjusting for potential confounders. Eighty infants were included. Giardia duodenalis and soil-transmitted helminths (STH) were the most frequent parasites. The median (interquartile range) levels were 2.87 μg/g (2.41-3.92) for S100A12 and 165.1 μg/g (66.0-275.6) for A1AT. Weak evidence of association was found between S100A12 levels and G. duodenalis (p = 0.080) and STH infections (p = 0.089), and between A1AT levels and parasitic infection of any etiology (p = 0.089), at 24-months of age. Significant associations between A1AT levels and wasting (p = 0.006) and stunting (p = 0.044) were found. Previous parasitic infections were not associated with fecal biomarkers at 24 months of age. To summarize, previous asymptomatic parasitic infections showed no association with intestinal barrier dysfunction. Notwithstanding, a tendency toward increased levels of the inflammatory biomarker was observed for current G. duodenalis and STH infections, and increased levels of the permeability biomarker were significantly associated with stunting and wasting.
Collapse
Affiliation(s)
- Marisol Garzón
- Tropical Clinic Teaching and Research Unit, Instituto de Higiene e Medicina Tropical, Universidade NOVA de Lisboa, Lisboa, Portugal
| | - Luis Pereira-da-Silva
- Research Unit, Centro Hospitalar de Lisboa Central, Lisboa, Portugal
- Woman, Children and Adolescent’s Medicine Teaching and Research Area, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
| | - Jorge Seixas
- Tropical Clinic Teaching and Research Unit, Instituto de Higiene e Medicina Tropical, Universidade NOVA de Lisboa, Lisboa, Portugal
| | - Ana Luísa Papoila
- Research Unit, Centro Hospitalar de Lisboa Central, Lisboa, Portugal
- NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
| | - Marta Alves
- Research Unit, Centro Hospitalar de Lisboa Central, Lisboa, Portugal
| | - Filipa Ferreira
- Tropical Clinic Teaching and Research Unit, Instituto de Higiene e Medicina Tropical, Universidade NOVA de Lisboa, Lisboa, Portugal
| | - Ana Reis
- Tropical Clinic Teaching and Research Unit, Instituto de Higiene e Medicina Tropical, Universidade NOVA de Lisboa, Lisboa, Portugal
| |
Collapse
|
|
41
|
Evans-Osses I, Mojoli A, Monguió-Tortajada M, Marcilla A, Aran V, Amorim M, Inal J, Borràs FE, Ramirez MI. Microvesicles released from Giardia intestinalis disturb host-pathogen response in vitro. Eur J Cell Biol 2017; 96:131-142. [DOI: 10.1016/j.ejcb.2017.01.005] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2016] [Revised: 12/23/2016] [Accepted: 01/11/2017] [Indexed: 11/17/2022] Open
|
|
42
|
Abstract
Functional dyspepsia (FD) is common and significantly impairs quality of life. Symptoms of FD are considered to originate from the gastroduodenal region, classified by the Rome criteria as disorders of brain-gut interaction without structural alteration. However, it is now apparent that FD is a number of syndromes, the epigastric pain syndrome (bothersome epigastric pain or epigastric burning) and the postprandial distress syndrome (with bothersome postprandial fullness or early satiation) and there are wide-ranging symptoms and severity. The origin of these troublesome symptoms is now considered to be a result of disrupted gastroduodenal neuropathophysiology. The complexity of the syndrome indicates that there must be different triggers, supported by the limited efficacy of the many treatments available. Current research based on evidence by association suggests that duodenal contents, including the duodenal microbiome, pathogens, and allergy may be triggers of FD. Recent studies have also shown that systemic responses of increased circulating lymphocytes and elevated proinflammatory cytokines and subtle inflammation in the duodenum may accompany the onset and persistence of symptoms. This inflammatory phenotype is characterized by innate inflammation, an eosinophil infiltrate in the duodenum in FD in those with postprandial distress syndrome. Routine histopathology practice does not quantify these cells so the status of FD is not yet appreciated as an inflammatory condition. Thus functional is becoming inflammatory and this breakthrough in understanding that functional does not necessarily mean no, but subtle pathology, may improve therapeutic options, which are currently aimed at symptom relief rather than targeted at underlying pathology.
Collapse
|
|
43
|
Genetics, Mucosal Inflammation and the Environment in Post-Infectious Chronic Gut Syndromes. ACTA ACUST UNITED AC 2016. [DOI: 10.1038/ajgsup.2016.14] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
|
|
44
|
Long-Term Consequences of Cryptosporidium and Giardia Gastroenteritis. CURRENT TROPICAL MEDICINE REPORTS 2016. [DOI: 10.1007/s40475-016-0078-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
|
|
45
|
Hanevik K. Editorial Commentary:Giardia lamblia–Pathogen or Commensal? Clin Infect Dis 2016; 63:798-9. [DOI: 10.1093/cid/ciw392] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2016] [Accepted: 06/06/2016] [Indexed: 11/12/2022] Open
|
|
46
|
Donowitz JR, Alam M, Kabir M, Ma JZ, Nazib F, Platts-Mills JA, Bartelt LA, Haque R, Petri WA. A Prospective Longitudinal Cohort to Investigate the Effects of Early Life Giardiasis on Growth and All Cause Diarrhea. Clin Infect Dis 2016; 63:792-7. [PMID: 27313261 PMCID: PMC4996141 DOI: 10.1093/cid/ciw391] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Accepted: 05/07/2016] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Growth stunting in children under 2 years of age in low-income countries is common. Giardia is a ubiquitous pathogen in this age group but studies investigating Giardia's effect on both growth and diarrhea have produced conflicting results. METHODS We conducted a prospective longitudinal birth cohort study in Dhaka, Bangladesh, with monthly Giardia and continuous diarrheal surveillance. RESULTS 629 children were enrolled within the first 72 hours of life, and 445 completed 2 years of the study. 12% of children were stunted at birth with 57% stunted by 2 years. 7% of children had a Giardia positive surveillance stool in the first 6 months of life, whereas 74% had a positive stool by 2 years. The median time to first Giardia positive surveillance stool was 17 months. Presence of Giardia in a monthly surveillance stool within the first 6 months of life decreased length-for-age Z score at 2 years by 0.4 (95% confidence interval, -.80 to -.001; P value .05) whereas total number of Giardia positive months over the 2-year period of observation did not. Neither variable was associated with weight-for-age Z score at 2 years. In our model to examine predictors of diarrhea only exclusive breastfeeding was significantly associated with decreased diarrhea (P value <.001). Concomitant giardiasis was neither a risk factor nor protective. CONCLUSIONS Early life Giardia was a risk factor for stunting at age 2 but not poor weight gain. Presence of Giardia neither increased nor decreased odds of acute all cause diarrhea.
Collapse
Affiliation(s)
- Jeffrey R Donowitz
- Division of Pediatric Infectious Diseases, Children's Hospital of Richmond at Virginia Commonwealth University
| | - Masud Alam
- Parasitology Laboratory, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka
| | - Mamun Kabir
- Parasitology Laboratory, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka
| | - Jennie Z Ma
- Department of Public Health Sciences, University of Virginia, Charlottesville
| | - Forida Nazib
- Department of Medicine and Vaccine Testing Center, The University of Vermont College of Medicine, Burlington
| | - James A Platts-Mills
- Division of Infectious Diseases and International Health, University of Virginia, Charlottesville
| | - Luther A Bartelt
- Division of Infectious Diseases, University of North Carolina-Chapel Hill
| | - Rashidul Haque
- Parasitology Laboratory, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka
| | - William A Petri
- Division of Infectious Diseases and International Health, University of Virginia, Charlottesville
| |
Collapse
|
|
47
|
El-Gayar EK, Mokhtar AB, Hassan WA. Study of the pathogenic potential of Dientamoeba fragilis in experimentally infected mice. Parasite Epidemiol Control 2016; 1:136-143. [PMID: 29988175 PMCID: PMC5991847 DOI: 10.1016/j.parepi.2016.05.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2016] [Revised: 05/14/2016] [Accepted: 05/15/2016] [Indexed: 11/22/2022] Open
Abstract
Dientamoebafragilis (D. fragilis) is a protozoan parasite whose pathogenic potential is still disputable. The aim of this study was to illustrate the pathogenicity of D. fragilis infection and to determine the infective dose for experimental mice infection. Three groups of mice (8/each) were orally inoculated with in vitro cultured D. fragilis. The infected groups (G1- G3) received 103, 105 and 4 × 106D. fragilis/0.5 ml culture, respectively. A control group (G4) only received parasite-free culture. Two weeks post-inoculation all mice were euthanized for histopathological examination. All mice of G3 (100%) and three mice of G2 (37.5%) were infected, and the results were confirmed by PCR and different staining methods. On the other hand, all mice from group G1 showed a completely negative result. Histopathological examination of the colon and caecum of the highly infected group G3 showed active colitis, with infiltration of mixed inflammatory cells such as eosinophils, neutrophils and lymphocytes within the lamina propria of the intestinal wall. The parasite was not invading the colonic mucosa. This study revealed that infection with D. fragilis is dose-dependent. Moreover, a dose of 105D. fragilis/mouse or higher is necessary to infect mice through the oral route. In addition, this route of infection, although non-invasive, can induce severe inflammatory changes to the colonic and caecal mucosa in experimentally infected mice.
Collapse
Affiliation(s)
- Eman K. El-Gayar
- Medical Parasitology Department, Faculty of Medicine, Suez Canal University, Egypt
| | - Amira B. Mokhtar
- Medical Parasitology Department, Faculty of Medicine, Suez Canal University, Egypt
| | - Wael A. Hassan
- Pathology Department, Faculty of Medicine, Suez Canal University, Egypt, Ismailia, 41522, Egypt
| |
Collapse
|
|
48
|
Di Genova BM, Tonelli RR. Infection Strategies of Intestinal Parasite Pathogens and Host Cell Responses. Front Microbiol 2016; 7:256. [PMID: 26973630 PMCID: PMC4776161 DOI: 10.3389/fmicb.2016.00256] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2015] [Accepted: 02/16/2016] [Indexed: 12/24/2022] Open
Abstract
Giardia lamblia, Cryptosporidium sp., and Entamoeba histolytica are important pathogenic intestinal parasites and are amongst the leading causes worldwide of diarrheal illness in humans. Diseases caused by these organisms, giardiasis, cryptosporidiosis, and amoebiasis, respectively, are characterized by self-limited diarrhea but can evolve to long-term complications. The cellular and molecular mechanisms underlying the pathogenesis of diarrhea associated with these three pathogens are being unraveled, with knowledge of both the strategies explored by the parasites to establish infection and the methods evolved by hosts to avoid it. Special attention is being given to molecules participating in parasite–host interaction and in the mechanisms implicated in the diseases’ pathophysiologic processes. This review focuses on cell mechanisms that are modulated during infection, including gene transcription, cytoskeleton rearrangements, signal transduction pathways, and cell death.
Collapse
Affiliation(s)
- Bruno M Di Genova
- Departamento de Microbiologia e Imunologia, Universidade Federal de São Paulo São Paulo, Brazil
| | - Renata R Tonelli
- Departamento de Microbiologia e Imunologia, Universidade Federal de São PauloSão Paulo, Brazil; Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Departamento de Ciências Biológicas, Universidade Federal de São PauloDiadema, Brazil
| |
Collapse
|
|
49
|
|
|
50
|
Miyamoto Y, Eckmann L. Drug Development Against the Major Diarrhea-Causing Parasites of the Small Intestine, Cryptosporidium and Giardia. Front Microbiol 2015; 6:1208. [PMID: 26635732 PMCID: PMC4652082 DOI: 10.3389/fmicb.2015.01208] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Accepted: 10/16/2015] [Indexed: 12/23/2022] Open
Abstract
Diarrheal diseases are among the leading causes of morbidity and mortality in the world, particularly among young children. A limited number of infectious agents account for most of these illnesses, raising the hope that advances in the treatment and prevention of these infections can have global health impact. The two most important parasitic causes of diarrheal disease are Cryptosporidium and Giardia. Both parasites infect predominantly the small intestine and colonize the lumen and epithelial surface, but do not invade deeper mucosal layers. This review discusses the therapeutic challenges, current treatment options, and drug development efforts against cryptosporidiosis and giardiasis. The goals of drug development against Cryptosporidium and Giardia are different. For Cryptosporidium, only one moderately effective drug (nitazoxanide) is available, so novel classes of more effective drugs are a high priority. Furthermore, new genetic technology to identify potential drug targets and better assays for functional evaluation of these targets throughout the parasite life cycle are needed for advancing anticryptosporidial drug design. By comparison, for Giardia, several classes of drugs with good efficacy exist, but dosing regimens are suboptimal and emerging resistance begins to threaten clinical utility. Consequently, improvements in potency and dosing, and the ability to overcome existing and prevent new forms of drug resistance are priorities in antigiardial drug development. Current work on new drugs against both infections has revealed promising strategies and new drug leads. However, the primary challenge for further drug development is the underlying economics, as both parasitic infections are considered Neglected Diseases with low funding priority and limited commercial interest. If a new urgency in medical progress against these infections can be raised at national funding agencies or philanthropic organizations, meaningful and timely progress is possible in treating and possibly preventing cryptosporidiosis and giardiasis.
Collapse
Affiliation(s)
- Yukiko Miyamoto
- Department of Medicine, University of California at San Diego, La Jolla CA, USA
| | - Lars Eckmann
- Department of Medicine, University of California at San Diego, La Jolla CA, USA
| |
Collapse
|