Aus dem Friedrich-Loeffler-Institut eingereicht über den Fachbereich Veterinärmedizin der Freien Universität Berlin Spatial Epidemiology of Rabies in Iran Inaugural-Dissertation zur Erlangung des Grades eines Doktors der Veterinärmedizin an der Freien Universität Berlin vorgelegt von Rouzbeh Bashar Tierarzt aus Teheran, Iran Berlin 2019 Journal-Nr.: 4015 'ĞĚƌƵĐŬƚŵŝƚ'ĞŶĞŚŵŝŐƵŶŐĚĞƐ&ĂĐŚďĞƌĞŝĐŚƐsĞƚĞƌŝŶćƌŵĞĚŝnjŝŶ ĚĞƌ&ƌĞŝĞŶhŶŝǀĞƌƐŝƚćƚĞƌůŝŶ ĞŬĂŶ͗ hŶŝǀ͘ͲWƌŽĨ͘ƌ͘:ƺƌŐĞŶĞŶƚĞŬ ƌƐƚĞƌ'ƵƚĂĐŚƚĞƌ͗ WƌŽĨ͘ƌ͘&ƌĂŶnj:͘ŽŶƌĂƚŚƐ ǁĞŝƚĞƌ'ƵƚĂĐŚƚĞƌ͗ hŶŝǀ͘ͲWƌŽĨ͘ƌ͘DĂƌĐƵƐŽŚĞƌƌ ƌŝƚƚĞƌ'ƵƚĂĐŚƚĞƌ͗ Wƌ͘<ĞƌƐƚŝŶŽƌĐŚĞƌƐ ĞƐŬƌŝƉƚŽƌĞŶ;ŶĂĐŚͲdŚĞƐĂƵƌƵƐͿ͗ ZĂďŝĞƐ͕DĂŶ͕ŶŝŵĂůƐ͕ŽŐƐ͕ƉŝĚĞŵŝŽůŽŐLJ͕ƌĂŝŶ͕/ŵŵƵŶŽĨůƵŽƌĞƐĐĞŶĐĞ͕/ƌĂŶ dĂŐĚĞƌWƌŽŵŽƚŝŽŶ͗Ϯϴ͘Ϭϯ͘ϮϬϭϵ ŝďůŝŽŐƌĂĨŝƐĐŚĞ/ŶĨŽƌŵĂƚŝŽŶĚĞƌĞƵƚƐĐŚĞŶEĂƚŝŽŶĂůďŝďůŝŽƚŚĞŬ ŝĞĞƵƚƐĐŚĞEĂƚŝŽŶĂůďŝďůŝŽƚŚĞŬǀĞƌnjĞŝĐŚŶĞƚĚŝĞƐĞWƵďůŝŬĂƚŝŽŶŝŶĚĞƌĞƵƚƐĐŚĞŶEĂƚŝŽŶĂůďŝͲ ďůŝŽŐƌĂĨŝĞ͖ ĚĞƚĂŝůůŝĞƌƚĞ ďŝďůŝŽŐƌĂĨŝƐĐŚĞ ĂƚĞŶ ƐŝŶĚ ŝŵ /ŶƚĞƌŶĞƚ ƺďĞƌ фŚƚƚƉƐ͗ͬͬĚŶď͘ĚĞх ĂďƌƵĨďĂƌ͘ /^E͗ϵϳϴͲϯͲϴϲϯϴϳͲϵϳϮͲϯ ƵŐů͗͘ĞƌůŝŶ͕&ƌĞŝĞhŶŝǀ͕͘ŝƐƐ͕͘ϮϬϭϵ ŝƐƐĞƌƚĂƚŝŽŶ͕&ƌĞŝĞhŶŝǀĞƌƐŝƚćƚĞƌůŝŶ ϭϴϴ ŝĞƐĞƐtĞƌŬŝƐƚƵƌŚĞďĞƌƌĞĐŚƚůŝĐŚŐĞƐĐŚƺƚnjƚ͘ ůůĞ ZĞĐŚƚĞ͕ ĂƵĐŚ ĚŝĞ ĚĞƌ mďĞƌƐĞƚnjƵŶŐ͕ ĚĞƐ EĂĐŚĚƌƵĐŬĞƐ ƵŶĚ ĚĞƌ sĞƌǀŝĞůĨćůƚŝŐƵŶŐ ĚĞƐ ƵĐŚĞƐ͕ ŽĚĞƌ dĞŝůĞŶ ĚĂƌĂƵƐ͕ǀŽƌďĞŚĂůƚĞŶ͘<ĞŝŶdĞŝůĚĞƐtĞƌŬĞƐĚĂƌĨŽŚŶĞƐĐŚƌŝĨƚůŝĐŚĞ'ĞŶĞŚŵŝŐƵŶŐĚĞƐsĞƌůĂŐĞƐŝŶŝƌŐĞŶĚĞŝŶĞƌ&Žƌŵ ƌĞƉƌŽĚƵnjŝĞƌƚŽĚĞƌƵŶƚĞƌsĞƌǁĞŶĚƵŶŐĞůĞŬƚƌŽŶŝƐĐŚĞƌ^LJƐƚĞŵĞǀĞƌĂƌďĞŝƚĞƚ͕ǀĞƌǀŝĞůĨćůƚŝŐƚŽĚĞƌǀĞƌďƌĞŝƚĞƚǁĞƌĚĞŶ͘ ŝĞ tŝĞĚĞƌŐĂďĞ ǀŽŶ 'ĞďƌĂƵĐŚƐŶĂŵĞŶ͕ tĂƌĞŶďĞnjĞŝĐŚŶƵŶŐĞŶ͕ ƵƐǁ͘ ŝŶ ĚŝĞƐĞŵ tĞƌŬ ďĞƌĞĐŚƚŝŐƚ ĂƵĐŚ ŽŚŶĞ ďĞƐŽŶĚĞƌĞ <ĞŶŶnjĞŝĐŚŶƵŶŐ ŶŝĐŚƚ njƵ ĚĞƌ ŶŶĂŚŵĞ͕ ĚĂƐƐ ƐŽůĐŚĞ EĂŵĞŶ ŝŵ ^ŝŶŶĞ ĚĞƌ tĂƌĞŶnjĞŝĐŚĞŶͲ ƵŶĚ DĂƌŬĞŶƐĐŚƵƚnjͲ'ĞƐĞƚnjŐĞďƵŶŐĂůƐĨƌĞŝnjƵďĞƚƌĂĐŚƚĞŶǁćƌĞŶƵŶĚĚĂŚĞƌǀŽŶũĞĚĞƌŵĂŶŶďĞŶƵƚnjƚǁĞƌĚĞŶĚƺƌĨĞŶ͘ dŚŝƐĚŽĐƵŵĞŶƚŝƐƉƌŽƚĞĐƚĞĚďLJĐŽƉLJƌŝŐŚƚůĂǁ͘ EŽƉĂƌƚŽĨƚŚŝƐĚŽĐƵŵĞŶƚŵĂLJďĞƌĞƉƌŽĚƵĐĞĚŝŶĂŶLJĨŽƌŵďLJĂŶLJŵĞĂŶƐǁŝƚŚŽƵƚƉƌŝŽƌǁƌŝƚƚĞŶĂƵƚŚŽƌŝnjĂƚŝŽŶŽĨ ƚŚĞƉƵďůŝƐŚĞƌ͘ ůůĞZĞĐŚƚĞǀŽƌďĞŚĂůƚĞŶͮĂůůƌŝŐŚƚƐƌĞƐĞƌǀĞĚ DĞŶƐĐŚƵŶĚƵĐŚsĞƌůĂŐϮϬϭϵ ŚŽƌŝŶĞƌ^ƚƌ͘ϴϱͲϭϬϭϭϵĞƌůŝŶ ǀĞƌůĂŐΛŵĞŶƐĐŚƵŶĚďƵĐŚ͘ĚĞʹǁǁǁ͘ŵĞŶƐĐŚƵŶĚďƵĐŚ͘ĚĞ Table of Contents 1 Introduction ........................................................................................................ 1 2 Literature Review ............................................................................................... 2 2.1 History of rabies............................................................................................. 2 2.2 Virus classification ......................................................................................... 4 2.3 Structure of the virion .................................................................................... 5 2.4 Replication of the rabies virus ....................................................................... 6 2.5 Pathogenesis of rabies .................................................................................. 7 2.6 Rabies symptoms in human .......................................................................... 8 2.7 Diagnosis in animals and humans ................................................................. 9 2.7.1 Diagnosis in animals ............................................................................... 9 2.7.2 Diagnosis in humans............................................................................... 9 2.8 Epidemiology of rabies ................................................................................ 10 2.9 Situation of rabies in Iran............................................................................. 13 2.10 Molecular epidemiology of rabies ................................................................ 15 2.11 Animal populations in Iran ........................................................................... 16 2.11.1 Livestock............................................................................................ 16 2.11.2 Wild carnivores .................................................................................. 17 2.12 Description of the study area (Iran) ............................................................. 18 2.13 Aim and Objectives...................................................................................... 19 3 Material and Methods....................................................................................... 20 3.1 Guideline to study and control rabies through the National Veterinary Organization.......................................................................................................... 20 3.2 Data collection............................................................................................. 20 3.2.1 Animal rabies data ................................................................................ 20 i 3.2.2 Human rabies data................................................................................ 21 3.2.3 Animal bite data .................................................................................... 21 3.2.4 Human population data......................................................................... 22 3.2.5 Animal population data ......................................................................... 22 3.3 Spatial analysis of rabies in Iran using a Geographical Information System (GIS) .................................................................................................................... 22 3.3.1 Creation of GIS maps ........................................................................... 23 3.4 Statistical software and data analysis methods ........................................... 23 4 Results ............................................................................................................. 24 4.1 Data Quality................................................................................................. 24 4.2 Animal rabies............................................................................................... 27 4.3 Temporal trends in animal rabies ................................................................ 37 4.4 Transmission of rabies by animals .............................................................. 43 4.5 Rabies in humans........................................................................................ 45 5 Discussion........................................................................................................ 46 5.1 Rabid animals.............................................................................................. 46 5.2 Geographical features of animal rabies in Iran ............................................ 55 5.3 Elements for rabies control in Iran ............................................................... 56 5.4 Rabies status in livestock in Iran ................................................................. 58 5.5 National network of rabies surveillance in Iran ............................................ 58 6 Conclusions...................................................................................................... 60 7 Summary.......................................................................................................... 62 Zusammenfassung................................................................................................ 63 8 Literature.......................................................................................................... 65 List of Figures ........................................................................................................... 77 List of Tables ............................................................................................................ 79 ACRONYMS AND ABBREVIATIONS....................................................................... 80 ii 9 Appendix .......................................................................................................... 82 9.1 Geographic location of the different provinces in Iran.................................. 82 9.2 The distribution of confirmed rabies cases in livestocks in Iran per province, 2000- 2013 (n=2676). ........................................................................................... 83 9.3 The distribution of confirmed rabies cases in carnivores in Iran per province, 2000- 2013 (n=1641). ........................................................................................... 85 9.4 Animals, raw data ........................................................................................ 87 9.5 Human Row Datasheet ............................................................................. 214 10 ACKNOWLEDGMENTS................................................................................. 216 Selbstständigkeitserklärung.................................................................................... 217 iii 1 Introduction Rabies infection is one of the fatal zoonotic encephalitis and caused by neurotropic viruses in the genus Lyssavirus, family Rhabdoviridae (ICTV 2015). Rabies virus is unique because it manages to exit in the saliva when its host is stimulated to bite - a mean accomplishment (Baer 1991). Rabies is usually caused by a bite from an infected mammal. The virus is introduced through the skin or mucus membrane. At first, it begins to replicate in the muscle, at the wound site. At this time it my be transported back to the wound or brain through reverse axonal transport, until it reaches the spinal cord. Some times, the virus may move across cell-to-cell junctions. At this stage, at first, certain symptoms of the disease occur, such as burning and pain at the site of the wound. Due to the spread of the virus to the brain and its proliferation there, encephalitis occurs. After proliferation in the brain,