Ph.D Thesis by Fatima Jahan Department of Zoology
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MALARIA EPIDEMIOLOGY IN DISTRICT BANNU, KHYBER PAKHTUNKHWA: IDENTIFYING GENOTYPES OF PLASMODIUM VIVAX IN THE REGION PH.D THESIS BY FATIMA JAHAN DEPARTMENT OF ZOOLOGY UNIVERSITY OF PESHAWAR Session (2009-2010) MALARIA EPIDEMIOLOGY IN DISTRICT BANNU, KHYBER PAKHTUNKHWA: IDENTIFYING GENOTYPES OF PLASMODIUM VIVAX IN THE REGION THESIS SUBMITTED TO THE DEPARTMENT OF ZOOLOGY, UNIVERSITY OF PESHAWAR, PESHAWAR, PAKISTAN IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY FATIMA JAHAN DEPARTMENT OF ZOOLOGY UNIVERSITY OF PESHAWAR KHYBER PAKHTUNKHWA, PAKISTAN Session (2009-2010) AUTHOR’S DECLARATION I, Fatima Jahan hereby state that my Ph.D thesis titled “Malaria Epidemiology in District Bannu, Khyber Pakhtunkhwa: Identifying Genotypes of Plasmodium Vivax in the Region” is my own work and has not been submitted to previously by me for taking any degree from this university of Peshawar, Pakistan or anywhere else in the country / world. At any time if my statement is found to be incorrect even after my graduation the university has the right to withdraw my Ph.D degree Student Name Fatima Jahan ACKNOWLEDGEMENTS I have no words to express my deepest gratitude to Almighty Allah, all praises for him, who guides us in darkness and helps in difficulties. First, I would like to extend my very deep appreciation, gratitude and sincere thanks to research supervisor Prof. Dr. Naheed Ali for giving me the opportunity to work on this project. I am grateful for her sound professional guidance and for encouraging me in all the stages of my dissertation. I am very thankful to my co-supervisor Assistant Prof. Dr. Nazma Habib khan, tremendous help during the study, informative advices of writing my dissertation and practical instructions during Lab work. Her approachability and ever inspiring encouragement played a vital role in the accomplishment of this study. Special thanks to Assistant Prof. Dr. Sobia wahid for her useful suggestions and support in this work. I am also thankful to Dr. Inayat Ali Shahjehan (Ex-chairman) and Dr. Syed Akram Shah (Chairman) Department of Zoology, University of Peshawar for their full support and valuable guidance. I would like to thanks Miss Ayesha kauser, Gule Tanzila for their advices and encouragement and always having inspiring words for me even in stressful situations during the study work. Also thankful to Dr. Shumaila Noreen for her useful suggestions. The field work was a difficult task and it would not have been possible without the cooperation and constant support of the laboratory and hospital staff. I would like to thanks Mr. Ikram Ullah (WCH, Bannu), Mr. Mujtaba (Siddique Lab. Bannu) for their valuable co-operation during sample collection. A special thanks to Mr. Zaki Ullah (Asst. Prof. Pharmacy Dept., University of Peshawar) for his full support during Lab work. I am grateful to Mr. Safeer Ullah Shah (National Centre of Excellence in Geology, University of Peshawar) for his co-operation. I also wish to thank Dr. Khalid Masud (Director LRH) for his full co-operation and support. Thank you to my office staff (Dr. Faisal Shehzad and Dr. Mujeeb Ur Rehman) and colleagues (Mahwish Khan, Marina Iqbal, Uzma Karim, Sikander Wadood, Arif Khan and Rashid Noor) who always support me during this tough route of PhD. Special gratitude for my friends Nazish Shah (Lecturer Swabi University) Farida Zai (Lecturer at COBAM, UOP), Humaira liaqat, Baseerat Ayesha and Ayesha Gul who constantly encouraging me during this task. A special thanks to my husband Ghulam Dastagir (Late) who sacrificed his precious time for my study. May Allah bless him with high Place in Jannah. I am particularly thankful to my brothers in Law (Mr. Imran Ullah khan, Farman Ullah khan and Abdul Samad) for their kind co-operation in this work. Finally, I am extremely thankful to my family members. I would like thanks my father Taj Muhammad Khan, mother, sisters (Surraya Jahan, Sadia Jahan, Bushra Jahan, Dr. Ruqqaya Jahan, Dr, Shahida Jahan, Bilques Jahan, Maimoona Jahan and Aiman Jahan) for providing constant source of inspiration and encouragement throughout my life and whose moral and financial support, understanding and irreplaceable love enabled me to bring my academic carrier to this stage. Last but not the least I would like to mention special thanks to my younger sister Dr. Asma Jahan for her love and support during my study. I prominently appreciate having you in my life. Fatima Jahan Contents TABLE OF CONTENTS ........................................................................................................... i ABSTRACT .............................................................................................................................. iv ABBREVIATIONS ................................................................................................................. vi LIST OF FIGURES ................................................................................................................. vii LIST OF TABLES .................................................................................................................. viii Chapter 1 INTRODUCTION ..................................................................................................... 1 1.1 Malaria ....................................................................................................................... 1 1.2 History of malaria ...................................................................................................... 2 1.3 Plasmodium; the parasite ........................................................................................... 4 1.3.1 Plasmodium Genome ......................................................................................... 5 1.3.2 Evolution of Plasmodium................................................................................... 6 1.3.3 Taxonomy ........................................................................................................ 11 1.3.4 Reservoirs of Plasmodium: .............................................................................. 12 1.4 Vector of Malaria ..................................................................................................... 12 1.4.1 Distribution of malaria vector .......................................................................... 13 1.5 Transmission & pathogenesis .................................................................................. 14 1.5.1 Vector and hosts ............................................................................................... 14 1.5.2 Transmission of malaria: .................................................................................. 16 1.5.3 Life cycle: ........................................................................................................ 16 1.5.4 Pathogenesis in vector host: ............................................................................. 19 1.5.5 Disease Pathogenesis in Human ...................................................................... 20 1.5.6 Pathogenesis of severe malaria ........................................................................ 23 1.5.7 Clinical representation of malaria .................................................................... 25 1.6 Recurrent or persistent malaria ................................................................................ 29 1.7 Immunity against parasite ........................................................................................ 30 1.8 Treatment and Prevention of Malaria ...................................................................... 30 1.8.1 Treatment ......................................................................................................... 30 1.8.2 Prevention ........................................................................................................ 32 1.9 Malaria vaccines ...................................................................................................... 33 1.10 Antimalarial drug resistance .................................................................................... 34 1.11 Worldwide malaria epidemiology ............................................................................ 35 1.12 Malaria epidemiology in Pakistan............................................................................ 39 1.13 Diagnosis ................................................................................................................. 45 1.13.1 MICROSCOPY ................................................................................................ 45 1.13.2 Rapid diagnostic Technique (RDT) ................................................................. 48 1.13.3 Polymerase chain reaction (PCR) .................................................................... 50 i 1.13.4 Serology ........................................................................................................... 54 1.14 Risk factors for malaria ............................................................................................ 55 1.14.1 Environmental factors ...................................................................................... 55 1.14.2 Vector related factors ....................................................................................... 58 1.14.3 Human related factors ...................................................................................... 59 1.15 Genetics of Plasmodium .......................................................................................... 61 1.16