The impact of helminth infection in patients with active tuberculosis

................................................................................................................................... 1 SUMMARY IN SWEDISH/SAMMANFATTNING PÅ SVENSKA ........................................... 3 LIST OF ORIGINAL PAPERS ...................................................................................................... 5 ABBREVIATIONS ........................................................................................................................ 7 BACKGROUND .......................................................................................................................... 10 Historical overview and global epidemiology of tuberculosis .................................................. 10 Mycobacterium tuberculosis ..................................................................................................... 10 Tuberculosis .............................................................................................................................. 10 Tuberculosis and HIV/AIDS ..................................................................................................... 11 Host susceptibility to tuberculosis............................................................................................. 12 Pathogenesis and host immune response to tuberculosis .......................................................... 13 The innate immune response to Mycobacterium tuberculosis .............................................. 13 The adaptive immune response during tuberculosis.............................................................. 14 The granuloma ....................................................................................................................... 15 Clinical characteristics of tuberculosis ...................................................................................... 16 Diagnosis of tuberculosis .......................................................................................................... 17 Treatment of tuberculosis .......................................................................................................... 18 Drug resistance in tuberculosis ................................................................................................. 19 Tuberculosis vaccines ............................................................................................................... 20 Classification, global epidemiology and public health impact of helminths ............................ 21 The host immune response to helminths ................................................................................... 22 The role of regulatory T-cells in health and helminth infection ............................................... 22 Helminth co-infection with HIV/AIDS ..................................................................................... 25 Helminths and non-infectious diseases ..................................................................................... 25 Impact of helminths on vaccine efficacy ................................................................................... 26 Helminth co-infection with tuberculosis ................................................................................... 27 AIMS............................................................................................................................................. 29 PATIENTS, MATERIALS AND METHODS ............................................................................. 30 Study setting............................................................................................................................... 30 Study participants (Paper I-V)................................................................................................... 33 Clinical and laboratory patient characteristics .......................................................................... 36 Baseline characteristics and the TB-score ............................................................................. 36 HIV testing and CD4+ cell counts ......................................................................................... 37 IgE, eosinophil cell count and Quantiferon measurement ..................................................... 37 Stool examination .................................................................................................................. 37 Sputum smear examination ................................................................................................... 38 Isolation of peripheral blood mononuclear cells (PBMCs) .................................................. 38 Analysis of regulatory T-cells by flow cytometry ................................................................. 38 Analysis of IFN-γ, IL-5 and IL-10 by ELISPOT .................................................................. 39 Statistics (Paper I-V) ................................................................................................................. 39 Ethical considerations ............................................................................................................... 40 RESULTS AND DISCUSSIONS (Paper I-V) ............................................................................. 42 CONCLUSIONS........................................................................................................................... 64 CONCLUDING REMARKS ........................................................................................................ 65 REFERENCES ............................................................................................................................. 68 ACKNOWLEDGEMENTS .......................................................................................................... 82