Disease Ecology and Epidemiology of Cutaneous Leishmaniasis Caused by Leishmania Tropica in Palestine
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Disease Ecology and Epidemiology of Cutaneous Leishmaniasis caused by Leishmania tropica in Palestine Thesis submitted in partial fulfillment of the requirements for the degree of “DOCTOR OF PHILOSOPHY” by Ikram A. Salah Submitted to the Senate of Ben-Gurion University of the Negev February 28, 2018 Beer-Sheva I Disease Ecology and Epidemiology of Cutaneous Leishmaniasis caused by Leishmania tropica in Palestine Thesis submitted in partial fulfillment of the requirements for the degree of “DOCTOR OF PHILOSOPHY” by Ikram A. Salah Submitted to the Senate of Ben-Gurion University of the Negev Approved by: __________________ Burt Kotler Nadav Davidovitch (Advisor) (Advisor) ____________________________________________ Dudy Bar-Zvi (Dean of the Kreitman School of Advanced Graduate Studies) February 28, 2018 Beer-Sheva II This work was carries under the supervision of: Prof. Burt Kotler Marco and Louise Mitrani Department of Desert Ecology The Swiss Institute for Dryland Environmental and Energy Research The Jacob Blaustein Institute for Desert Research Ben-Gurion University of the Negev Prof. Nadav Davidovitch Department of Health System Management School of Public Health Faculty of Health Science Ben-Gurion University of the Negev III Research-Student's Affidavit when Submitting the Doctoral Thesis for Judgment I Ikram A. Salah, whose signature appears below, hereby declare that (Please mark the appropriate statements): X I have written this Thesis by myself, except for the help and guidance offered by my Thesis Advisors. X The scientific materials included in this Thesis are products of my own research, culled from the period during which I was a research student. This Thesis incorporates research materials produced in cooperation with others, excluding the technical help commonly received during experimental work. Therefore, I am attaching another affidavit stating the contributions made by myself and the other participants in this research, which has been approved by them and submitted with their approval. Date: February 19, 2018 Student's name: Ikram A. Salah Signature: IV ACKNOWLEDGEMENTS A special and profound thanks to my Mom, my sister Hala Salah, sisters, brothers, nephews, nieces and the rest of my extended family for theirs help, encouragement and support. How can I forget my angel who supports, encourages and stands by me to pass all difficult days. I would like to express my gratitude to my supervisor Prof. Burt Kotler, for his good advice, encouragement and support, and for his continuous belief in me. I am truly thankful to my supervisor Prof. Nadav Davidovitch for opening me the window to the enthralling field of Eco- health, and for his encouragement and support. I also thank my committee members Yael Lubin, Hadas Hawlena, and Alon Warburg. Many thanks to my lab mates Elsita Kiekebusch, Austin Dixon, Jorge Menezes, and Stuart Summerfield, who provide input, discussion, help, and encouragement all the time. Thanks to the whole community of Kisan Village, Arab Ar-Rashaiyda village, and Arab Al ‘Azazma in Bethlehem District. Thanks to the whole community of Tubas District. Special thanks to Taleb Qasal, Ezat Dragmeah family, and Mohammad Shriam family who were hosting me during the time of the field work. Many thanks to Taleb Qasal, Saad Dragmeah, Ahmad Othman, and Mahmood Bsharat who were helping me setting the traps and going with me house by house to conduct the interviews during the field work. I am indebted to Prof. Alon Warburg for supporting, advising and making the research possible by providing most of the equipment for sand fly collection, and allowing me to conduct all molecular analysis for sand flies in his laboratory. Many thanks to Dr. Amer Al-Jawabreh for teaching me the basis of molecular biology, and giving me the courage to learn all the procedures of collecting, analyzing the patient’s samples. Last but not least, I am grateful to Dr. Ibrahim Abbasi for teaching me how to identify blood meal in sand flies, thanks for all support, help, and patience. V This study was made possible by a generous grant from Ben-Gurion University president’s Prof. Rivka Carmi, Georg Waechter Memorial Foundation, and Science Training Encouraging Peace – Graduate Training Program (STEP-GTP). And finally, thank you all. With love I dedicate this work to the person who encouraged me all the time, my Father, May his soul rest in peace. Also to the women who was dreaming all the time to have an educated daughter, my Mother, May God grant her good health. "Save the World from Diseases" (Ibn Sina – Avicenna) "O men! Here is a parable set forth! Listen to it! Those on whom, besides Allah, ye call, cannot create (even) a fly, if they all met together for the purpose! And if the fly should snatch away anything from them, they would have no power to release it from the fly. Feeble are those who petition and those whom they petition!" (Chapter 22, Al-Hajj: Verse 73) VI Table of Constants Research-Student's Affidavit for Submitting the Doctoral Thesis for Judgment IV Acknowledgements V Table of Contents VII List of Figures and Tables XII List of Abbreviation and Terms XVI Abstract XVII CHAPTER ONE: INTRODUCTION 1 1.1.0.0.0. General background 1 1.2.0.0.0. Leishmaniasis 6 1.2.1.0.0. Geographical distribution 6 1.2.2.0.0. The disease 6 1.2.2.1.0. Cutaneous leishmaniasis (CL) 7 1.2.2.2.0. Mucocutaneous leishmaniasis (MCL) 7 1.2.2.3.0. Visceral leishmaniasis (VL) 7 1.2.2.4.0. Post Kala-Azar dermal leishmaniasis (PKDL) 8 1.3.0.0.0. The causative agent 8 VII 1.3.1.0.0. The parasite 8 1.3.2.0.0. The life cycle: 8 1.3.3.0.0. Transmission 8 1.4.0.0.0. The vector: Phlebotomine Sandflies (Diptera: Psychodidae) 9 1.4.1.0.0. Feeding behavior 9 1.4.2.0.0. Distributions of sand flies 9 1.4.3.0.0. Population dynamic and seasonal changes 10 1.4.4.0.0. Public health importance of sand fly distributions 10 1.4.5.0.0. Control methods of Sand flies 11 1.5.0.0.0. The Reservoir Host: Rock Hyrax Procavia capensis ( Hyracoidea: 12 Procaviidae) 1.5.1.0.0. Rock Hyrax distribution 12 1.5.2.0.0. Rock Hyrax, Reservoir host of Leishmaniasis 12 1.6.0.0.0. Leishmaniasis in Palestine 13 1.7.0.0.0. Eco-epidemiological approach 14 1.8.0.0.0. Overall aim and specific objectives 15 1.8.1.0.0. Overall aim 15 1.8.2.0.0. Specific objectives 15 1.9.0.0.0. General and specific hypothesis 16 1.9.1.0.0. General hypothesis 16 VIII 1.9.2.0.0. Specific hypothesis 16 1.10.0.0.0. Innovation aspects 16 CHAPTER TWO: MATERIALS AND METHODS 17 2.1.0.0.0. Sand fly sampling at the Bethlehem study sites 17 2.1.0.1.0. Study area 17 2.1.0.2.0. Data collection 17 2.1.1.0.0. Comparison of sand fly activity between KIS, AAR, AZA in 2013 17 2.1.1.1.0. Comparison of sand fly densities among the three sites 17 2.1.1.2.0. Comparison in species for males among the three sites 19 2.1.1.3.0. Host blood species identification and Leishmania parasite detection 19 2.1.1.3.1. Sand flies identification 19 2.1.1.3.2. DNA extraction 19 2.1.1.3.3. Blood meal identification and parasite detection 20 2.1.2.0.0. Comparison of Sand fly activity between AAR, AZA in 2014 20 2.1.0.3.0. Statistical analysis 20 2.2.0.0.0. Epidemiological Investigation in the Tubas study sites 21 2.2.0.1.0. Study area 21 2.2.0.2.0. Data collection 21 2.2.0.3.0. Statistical analysis 23 IX 2.3.0.0.0. Sand fly transects for sampling the Tubas study site 23 2.3.0.1.0. Study area 23 2.3.0.2.0. Data collection 24 2.3.1.0.0. Sand fly density 24 2.3.2.0.0. Sand fly species identification 25 2.3.3.0.0. Leishmania parasite detection 26 2.3.4.0.0. Host blood species identification 26 2.3.0.3.0. Statistical analysis 26 CHAPTER THREE: RESULTS 27 3.1.0.0.0. Sand fly sampling at the Bethlehem study sites 27 3.1.1.0.0. Comparison of sand fly activity between KIS, AAR, AZA in 2013 27 3.1.1.1.0. Comparison of sand fly densities among the three sites 27 3.1.1.2.0. Comparison in species for males among the three sites 31 3.1.1.3.0. Host blood species identification and Leishmania parasite detection 33 3.1.2.0.0. Comparison of Sand fly activity between AAR, AZA in 2014 38 3.2.0.0.0. Epidemiological Investigation in the Tubas study sites 39 3.2.1.0.0. Demographic characteristics 39 3.2.2.0.0. Clinical information 43 3.2.3.0.0. Human behavior 45 X 3.2.4.0.0. Personal protection 45 3.2.5.0.0. Topography and house information 48 3.2.6.0.0. Information about vector and reservoir 48 3.3.0.0.0. Sand fly transects for sampling the Tubas study site 51 3.3.1.0.0. Sand fly density 51 3.3.2.0.0. Sand fly species identification 52 3.3.3.0.0. Leishmania parasite detection 55 3.3.4.0.0.