Loc Le1,2, Sabiha Khatoon1,2, Paola Jiménez1,2, Christopher Peterson2, Rebecca Kernen2, Weidong Zhang1,2, Adebayo J Molehin1,2, Samra Lazarus1,2, Justin Sudduth1,2, Jordan May1,2,3, Souvik Karmakar4, Juan U Rojo5, Gul Ahmad6, Workineh Torben7, David Carey8, Roman F Wolf8,9, James F Papin8, Afzal A Siddiqui10,11. 1. Center for Tropical Medicine and Infectious Diseases, Texas Tech University Health Sciences Center, Lubbock, TX, USA. 2. Department of Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA. 3. Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX, USA. 4. Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. 5. Department of Molecular, Cellular and Biomedical Sciences, University of New Hampshire, Durham, NH, USA. 6. Department of Natural Sciences, Peru State College, Peru, NE, USA. 7. Department of Biological Sciences, Louisiana State University, Alexandria, LA, USA. 8. Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. 9. Oklahoma City VA Health Care System, Oklahoma City, OK, USA. 10. Center for Tropical Medicine and Infectious Diseases, Texas Tech University Health Sciences Center, Lubbock, TX, USA. afzal.siddiqui@ttuhsc.edu. 11. Department of Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA. afzal.siddiqui@ttuhsc.edu.
Abstract
BACKGROUND: Schistosomiasis continues to inflict significant morbidity and mortality in the tropical and subtropical regions of the world. The disease endemicity overlaps with the transmission of other parasitic diseases. Despite the ubiquity of polyparasitism in tropical regions, particularly in rural communities, little is known about the impact of multiple helminth infections on disease progression. In this pilot study, we describe the influence of chronic Trichuris trichiura infection on Schistosoma mansoni egg-induced hepatopathology in infected baboons. METHODS: Baboons with or without underlying whipworm infection were challenged with S. mansoni cercariae to establish schistosomiasis. Adult S. mansoni worms were recovered by perfusion and enumerated, hepatic granulomas were quantified via light microscopy, and transcriptional profiling of tissues were completed using RNA sequencing technologies. RESULTS: Co-infection with both S. mansoni and T. trichiura resulted in higher female schistosome worm burden and significantly larger liver granuloma sizes. Systems biology analyses of peripheral blood mononuclear cells (PBMC) revealed pathways associated with increased liver damage in co-infected baboons. CONCLUSIONS: Underlying chronic whipworm infection intensified schistosome egg-induced liver pathology in infected baboons. RNA-Seq analysis provided insight into pathways associated with increased liver damage, corroborating histological findings.
BACKGROUND:Schistosomiasis continues to inflict significant morbidity and mortality in the tropical and subtropical regions of the world. The disease endemicity overlaps with the transmission of other parasitic diseases. Despite the ubiquity of polyparasitism in tropical regions, particularly in rural communities, little is known about the impact of multiple helminth infections on disease progression. In this pilot study, we describe the influence of chronic Trichuris trichiura infection on Schistosoma mansoni egg-induced hepatopathology in infected baboons. METHODS:Baboons with or without underlying whipworm infection were challenged with S. mansoni cercariae to establish schistosomiasis. Adult S. mansoni worms were recovered by perfusion and enumerated, hepatic granulomas were quantified via light microscopy, and transcriptional profiling of tissues were completed using RNA sequencing technologies. RESULTS: Co-infection with both S. mansoni and T. trichiura resulted in higher female schistosome worm burden and significantly larger liver granuloma sizes. Systems biology analyses of peripheral blood mononuclear cells (PBMC) revealed pathways associated with increased liver damage in co-infected baboons. CONCLUSIONS: Underlying chronic whipworm infection intensified schistosome egg-induced liver pathology in infected baboons. RNA-Seq analysis provided insight into pathways associated with increased liver damage, corroborating histological findings.