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Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases CONTENTS ………..……………………………………………………………. 2 Introduction ……………………………………………………………………………………. 3 Curriculum ……………………………………………………………………………………… 4 Block Team ………………………………………………………………………................... 6 Facilitators ……………………………………………………………………………………… 7 Time Table ………………….…………………………………………………………………… 8 Meeting of Students representatives ………………………………………………………… 17 Meeting of The Facilitators…………………………………………………………………. 17 Assessment method …………………………………………………………………………... 17 Student Project ………………………………………………………….....…………………. 18 Learning Program …………………………………………………………………………….. 20 Curriculum Mapping …………………………………………………………………………... 75 Reference ……………………………………………………………………………………… 76 Table of contents Udayana University Faculty of Medicine, DME, 2016 1 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases INTRODUCTION Due to the application of integrated curriculum at the Faculty of Medicine Udayana University, the discipline-based subjects of the previous curriculum such as Biology, Anatomy, Physiology, Internal Medicine, etc have been integrated and incorporated into several blocks. One of these blocks is Infections and Infectious Diseases. In this block will be explained in general about pathogenesis, pathophysiology, sign, symptoms, clinical features, diagnosis, and management of certain infectious diseases commonly occur in community. This book aims to give general information for medical students about infections and infectious diseases and important for facilitators and resource person while facilitating or guiding the students in learning process. This study guide consists of general information on learning time table, block team members, facilitators, and the core curriculum including learning outcomes, learning situations, learning tasks and self-evaluation items. The block Infection and Infectious Diseases has the equivalent of (six) credits. As a block of six credits, the learning processes will be carried out for 38 days starts from September, 1st 2016 as shown in the Time Table. The examination for Basic Microbiology and Parasitology will be conducted on 30th of September 2016, followed by lecture of infection and infectious disease. Examination for infection and infectious disease will be held on 31st of October 2016. Final mark of this block is combination between result of basic and clinical examination. During the 38 days of learning activities, the students will discuss several topics in varied forms of learning situations such as independent learning, small group discussion, lecture, and skill lab. More than half of the learning material must be learned independently and in small group discussions. A lecture is given only to emphasize crucial things or objectives of material and to prepare the students before discussion. For small group discussion, the students will be given learning tasks to solve and discuss. After discussion, students also have to evaluate their learning progress independently (self assessment). From this block, we hope every medical student have knowledge and skill to diagnose and manage infections and certain infectious diseases commonly occur in community, as a frontline in community health. Since the integrated curriculum of the Faculty of Medicine Udayana University is still in progress, this Study Guide will also, naturally, have some revisions in the future. Therefore, we kindly invite readers to give any comments or suggestions for its improvement and development. Planners Udayana University Faculty of Medicine, DME, 2016 2 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases CURRICULUM OF THE BLOCK AIMS To comprehend the biology of the infectious diseases To apply and interpret common laboratory diagnosis of infectious diseases To diagnose and manage common infectious diseases To carry out basic immunization in children LEARNING OUTCOMES Comprehend the practical and clinical implications of the biology of infection Apply the general principles of approach to patients with infectious diseases Apply and interpret common laboratory diagnosis of common infectious diseases Apply the basic principles of immunization in children Diagnose and manage common bacterial infections (common Gram positive and negative, spirochetal) Diagnose and manage common parasitic infections (common nematode, trematode, cestode, and protozoal infections) Diagnose and manage common fungal infections Clinically diagnose and manage common viral infections (caused by common respiratory virus, herpesvirus, arbovirus) Clinically diagnose and manage Infection in pregnancy (TORCH) CURRICULUM CONTENT 1. The biology of infection: bacterial, viral, fungal and parasitic. a. Principles of bacterial infections such as Staphylococci, Streptococci, Neisseria, Salmonella, Vibrio, anaerobic bacteria¸ Leptospira, Mycobacteria, Gram positive bacilli) b. Principles of viral infections such as respiratory virus (influenza virus, mumps, measles), retrovirus (HIV), herpesvirus (HSV 1, HSV 2, VZV, arbovirus (dengue virus, Japanese B encephalitis virus). c. Principles of fungal infections such as Candida, Pneumocytis jiroveci, Histoplasma, Cryptococcus d. Principles of parasitic infections such as Plasmodium, Toxoplasma gondii, Entamoeba histolytica and soil transmitted helminthes. 2. General approach to the patients with infection such as: a. Clinical manifestations (local and systemic infections) b. Laboratory examination to support diagnosis of infections i.e. Microbiological examination, Parasites examination, Clinical pathology examination, Pathology examination and Imaging examination 3. Management patients with infection such as: a. Common bacterial infections such as bacterial meningitis, typhoid fever,diarrhea, endocarditis, diphtheria, tetanus, food poisoning, genital gonorrhoeae, non gonococcal urethritis, etc. b. Common parasitic infections such as malaria, amoebiasis, toxoplasmosis. c. Common fungal infection such as dermatophytosis, systemic candidiasis, histoplasmosis, cryptococcosis, pneumocytis jiroveci pneumonia. Udayana University Faculty of Medicine, DME, 2016 3 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases d. Common viral infections such as mumps, measles, influenza (especially H5N1), SARS, varicella, herpes labialis, herpes genitalis, dengue fever, Japanese B encephalitis, and HIV. 4. Immunization in children. 5. Infection in pregnancy Udayana University Faculty of Medicine, DME, 2016 4 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases PLANNERS TEAM No Name Departement Phone Internal Medicine 08123815025 1 dr. Made Susila Utama, Sp.PD-KPTI 2 dr. Putu Yuliandari, S.Ked Microbiology 089685415625 3 dr NN Dwi Fatmawati, Sp.MK, Ph.D Microbiology 087862200814 4 Dr. dr. Made Sudarmaja, M.Kes Parasitology 08123953945 5 dr. Putu Gede Sudira, Sp.S DME 081805633997 LECTURERS NO 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. NAME Prof. Dr. dr. Tuti Parwati Merati, SpPD, KPTI-FINASIM Prof.Dr. dr. Raka Sudewi, Sp.S (K) dr. Made Susila Utama, Sp.PD dr. Agus Somia, SpPD dr. AA Yuli Gayatri, Sp.PD dr. Ni Made Dewi Dian Sukmawati, Sp.PD dr W. Gustawan,M.Sc., Sp.A dr. Made Bagiada, Sp.PD-KP Dr. dr. Wayan Sudhana, SpPD-KGH dr. Ratih Karna, Sp.KK Dr. dr. IB Fajar Manuaba, SpOG dr. Luh Ariwati dr. Kadek Swastika, M.Kes Dr. dr. Made Sudarmaja, M.Kes dr NN Dwi Fatmawati, Sp.MK, Ph.D Dr. dr. Sri Budayanti, Sp.MK Dr. dr. I Dewa Made Sukrama, M.Si, Sp.MK (K) dr. Made Agus Hendrayana, M.Ked I.B. Nyoman Putra Dwija, S.Si, M.Biotech Udayana University Faculty of Medicine, DME, 2016 DEPT Internal Medicine (Tropical Disease) Neurology Internal Medicine (Tropical Disease) Internal Medicine (Tropical Disease) Internal Medicine (Tropical Disease) Internal Medicine (Tropical Disease) Pediatri Pulmonology Internal Medicine (Nefrology) Dermatology & Venerology Obstetric & Gynecology Parasitology Parasitology Parasitology Microbiology Microbiology PHONE 08123806626 0816710244 08123815025 08123989353 08123803985 081805656501 08123848241 08123607874 08123914095 081337808844 081558101719 08123662311 08124649002 08123953945 087862200814 08583711398 Microbiology 081338291965 Microbiology 08123921590 Microbiology 08179747502 5 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases FACILITATORS (REGULAR CLASS) NO 1 NAME dr. Ni Made Susilawathi, Sp.S GROUP 1 DEPT Neurology PHONE 08124690137 2 dr. Ketut Agus Somia, Sp.PDKPTI dr. Tjok Istri Anom Saturti, Sp.PD dr. Putu Sudira, Sp.S 2 089617587075 4 Internal Medicine Internal Medicine DME dr. Agus Roy Rusly HH, Sp.BERE dr. IA Dewi Wiryanthini, M.Biomed dr. IN Gede Wardana, M. Biomed Prof. Dr. dr. I Putu Adiatmika, M.Ked dr. I Wayan Juli Sumadi, Sp.PA 5 Surgery 081239990399 6 Biochemistry 081239990399 7 Anatomy 087860405625 8 Physiology 08123811019 9 082237407778 dr. IA Kusuma Wardani, Sp.KJ, MARS 10 Patology Anatomy Psychiatry 3 4 5 6 7 8 9 10 3 082145854167 081805633997 08123813831 VENUE 3nd floor: R.3.09 3nd floor: R.3.10 3nd floor: R.3.11 3nd floor: R.3.12 3nd floor: R.3.13 3nd floor: R.3.14 3nd floor: R.3.15 3nd floor: R.3.16 3nd floor: R.3.17 3nd floor: R.3.19 FACILITATORS (ENGLISH CLASS) NO GROU P 1 DEPT PHONE VENUE ENT 081338701878 2 Forensik 08123988486 3 Surgery 08179201958 4 Pediatry 081337072141 5 dr. I Wayan Niryana, Sp.BS, M.Kes dr. Ni Nyoman Metriani Nesa, Sp.A, M.Sc Dr. dr. BK Satriyasa, M.Repro 5 Pharmacology 087777790064 6 Dr. dr. GN Indraguna P 6 IKK IKP 08123816424 7 7 Cardiology 8 dr. Made Satria Yudha Dewangga, SpJP dr. I Wayan Sugiritama, M.Kes 8 Histology 081805057315/ 082163500096 08164732743 9 dr. Tjahya Aryasa EM, Sp.An 9 Anesthesiology 081339713553 10 Desak Ernawati, S.Si PGPharm, M.Pharm,Ph.D 10 Pharmasi 081237753646 3nd floor: R.3.09 3nd floor: R.3.10 3nd floor: R.3.11 3nd floor: R.3.12 3nd floor: R.3.13 3nd floor: R.3.14 3nd floor: R.3.15 3nd floor: R.3.16 3nd floor: R.3.17 3nd floor: R.3.19 1 2 3 4 NAME dr. Komang Andi Dwi Saputra, Sp.THT-KL dr. Henky, Sp.F, M.Beth Udayana University Faculty of Medicine, DME, 2016 6 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases TIME-TABLE (Block Basic Microbiology, Parasitology, Infection and infectious Diseases) DAY/ DATE 1 Thursday Sept 1st 2016 2 Friday, Sept 2nd 2016 3 Monday, Sept 5th 2016 Time Regular Class English Class 08.00-08.30 09.00-09.30 08.30-09.00 09.30-10.00 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 12.30-14.00 10.00-11.30 14.00-14.30 15.00-15.30 14.30-15.00 15.30-16.00 08.00-08.30 09.00-09.30 08.30-09.00 09.30-10.00 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 12.30-14.00 10.00-11.30 14.00-14.30 Topic Lecture 1 Introduction of block Basic Infection and Infectious Diseases Lecture 2 General Parasitology Learning situation Introduction of the Block Individual learning Small group discussion Individual learning Plenary Session Place PIC Class room Prof. Dr. dr. Tuti Parwati Merati, SpPD, KPTI Dr. dr. Made Sudarmaja, M.Kes Disc. Room Facilitator Class room Prof. Dr. dr. Tuti Parwati Merati, SpPD, KPTI Dr. dr. Made Sudarmaja, M.Kes Dr. dr. I Dewa Made Sukrama, M.Si, Sp.MK dr. Made Agus Hendrayana, M.Ked Plenary Session Class room Lecture 3 Introduction of Microbiology Lecture Class room Lecture 4 Patogenesis of bacterial infection Lecture Class room Disc. Room Facilitator 15.00-15.30 Individual learning Small Group Discussion Individual learning Plenary Class Room 14.30-15.00 15.30-16.00 Plenary Class Room 08.00-08.30 09.00-09.30 Lecture 5 Diagnosis of Malaria Lecture Class Room 08.30-09.00 09.30-10.00 Lecture 6 Diagnosis of Filariasis Lecture Class room Dr. dr. I Dewa Made Sukrama, M.Si, Sp.MK dr. Agus Hendrayana, M.Ked Dr. dr. Made Sudarmaja, M.Kes Dr. dr. Made Sudarmaja, M.Kes 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 Disc. Room 12.30-14.00 10.00-11.30 Individual Learning Small group discussion Individual Udayana University Faculty of Medicine, DME, 2016 Facilitator 7 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases DAY/ DATE 4 Friday Sept 9th 2016 5 Tuesday, Sept 13th 2016 6 Wednesday, Sept 14th 2016 7 Thursday Sept 15th 2016 8 Monday, Sept 19th 2016 Time Regular Class English Class 14.00-15.00 15.00-16.00 08.00-09.00 09.00-10.00 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 12.30-14.00 10.00-11.30 14.00-15.00 08.00-09.00 15.00-16.00 09.00-10.00 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 12.30-14.00 10.00-11.30 14.00-15.00 15.00-16.00 08.00-09.00 09.00-10.00 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 12.30-14.00 10.00-11.30 14.00-15.00 15.00-16.00 08.00-09.00 09.00-10.00 09.00-10.30 13.30-15.00 10.30-12.00 10.00-11.30 12.30-14.00 15.00-16.00 08.00-09.00 09.00-10.00 Topic Lecture 7,8,9 Toxoplasmosis, amoebiasis, and systemic fungal infection Lecture 10, 11 Ascariasis, Trichuriasis Lecture 12,13,14 Hookworm infection, Strongyloidiasis, Enterobiasis Learning situation Place PIC learning Plenary Class room Lecture Class Room Dr. dr. Made Sudarmaja, M.Kes dr. Luh Ariwati Disc. Room Facilitator Class room Class room dr. Luh Ariwati dr. Luh Ariwati Individual Learning Small group discussion Individual learning Plenary Lecture Individual learning Small group discussion Individual learning Plenary Session Lecture Individual learning Small group discussion Individual learning Plenary Session Lecture 15,16 Larva migrans, Pediculosis Lecture 17,18,19 Schistosomiasi, Taeniasis, Sistisercosis Udayana University Faculty of Medicine, DME, 2016 Disc. Room Facilitator Class room dr. Luh Ariwati Class room Dr. dr. Made Sudarmaja, M.Kes Disc. Room Facilitator Class room Dr. dr. Made Sudarmaja, M.Kes dr. Kadek Swastika, M.Kes Facilitator Individual learning Small group discussion Individual learning Plenary Session Disc. Room Lecture Class room Class room dr. Kadek Swastika, M.Kes dr. Kadek Swastika, M.Kes 8 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases DAY/ DATE 9 Tuesday Sept 20th 2016 10 Tuesday Sept 21st 2016 11 Thursday, Sept 22nd 2016 12 Friday, Sept 23rd 2016 Time Regular Class English Class 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 12.30-14.00 10.00-11.30 14.00-15.00 15.00-16.00 08.00-16.00 08.00-16.00 08.00-08.30 09.00-09.30 08.30-09.00 09.30-10.00 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 12.30-14.00 10.00-11.30 14.00-14.30 15.00-15.30 14.30-15.00 15.30-16.00 08.00-09.00 09.00-10.00 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 12.30-14.00 10.00-11.30 14.00-15.00 15.00-16.00 08.00-09.00 09.00-10.00 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 Topic Learning situation Individual learning Small group discussion Individual learning Plenary Session STUDENT PROJECT (REGULER CLASS) Lecture 20, 21 Gram positive and negative bacteria Lecture 22: Mycobacterium Lecture 25, 26 RNA virus, Zoonosis Udayana University Faculty of Medicine, DME, 2016 Facilitator Class room dr. Kadek Swastika, M.Kes Evaluator & Fasilitator Teather Room Class room Lecture Class room Facilitator Class room dr. Made Agus Hendrayana, M.Ked IB Nyoman Putra Dwija, S.Si, M.Biotech Dr. dr. Ni Nyoman Sri Budayanti, Sp.MK Class room Lecture Class room Lecture Individual learning Small group discussion dr. Made Agus Hendrayana, M.Ked IB Nyoman Putra Dwija, S.Si, M.Biotech Disc. Room Plenary Session Individual learning Small group discussion Individual learning Plenary PIC Disc. Room Lecture Individual learning Small group discussion Individual learning Plenary Session Lecture 23, 24 Pathogenesis of viral infection, DNA virus Place Disc. Room Facilitator Class room Dr. dr. Ni Nyoman Sri Budayanti, Sp.MK Dr. dr. Ni Nyoman Sri Budayanti, Sp.MK Class room Disc. Room Facilitator 9 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases DAY/ DATE 13 Monday, Sept 26th 2016 14 Tuesday, Sept 27th 2016 15 Wednesday, Sept 28th 2016 Time Regular Class English Class 12.30-14.00 10.00-11.30 14.00-15.00 15.00-16.00 08.00-09.00 09.00-10.00 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 12.30-14.00 10.00-11.30 14.00-15.00 15.00-16.00 08.00-08.30 09.00-09.30 08.30-09.00 09.30-10.00 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 12.30-14.00 10.00-11.30 14.00-14.30 15.00-15.30 14.30-15.00 15.30-16.00 08.00-09.00 09.30-10.00 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 12.30-14.00 10.00-11.30 Learning situation Topic Lecture 27, 28 Specimen collection Microbial identification & Antimicrobial Sensitivity Test (AST) Place PIC Individual learning Plenary Class room Lecture Class room Dr. dr. Ni Nyoman Sri Budayanti, Sp.MK dr. Ni Nengah Dwi Fatmawati, Sp.MK, Ph.D Individual learning Small group discussion Disc. Room Facilitator MIDDLE BLOCK MEETING Plenary Lecture 29 Mechanism of action and resistance of antibiotic Lecture 30 Biosafety & Biosecurity Lecture Class room IB Nyoman Putra Dwija, S.Si, M.Biotech Disc. Room Facilitator Plenary Class room dr. Ni Nengah Dwi Fatmawati, Sp.MK, Ph.D Plenary Class room IB Nyoman Putra Dwija, S.Si, M.Biotech Lecture Class room Dr. dr. I Dewa Made Sukrama, M.Si, Sp.MK Disc. Room Facilitator Lecture Individual learning Small group discussion Individual learning Lecture 31, 32 Health careassociated infection Anaerob bacteria & Spirochaeta Udayana University Faculty of Medicine, DME, 2016 dr. Ni Nengah Dwi Fatmawati, Sp.MK, Ph.D dr. Ni Nengah Class room Dwi Fatmawati, Sp.MK, Ph.D Individual learning Small group discussion Individual learning 10 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases DAY/ DATE Thursday, Sept 29th 2016 Friday, Sept 30th 2016 16 Monday, Oct 3rd 2016 17 Tuesday, Oct 4th 2016 18 Wednesday, Oct 5th 2016 19 Thursday, Oct 6th 2016 Time Regular Class English Class 14.00-15.00 15.00-16.00 Learning situation Topic Plenary Place PIC Class room Dr. dr. I Dewa Made Sukrama, M.Si, Sp.MK SILENT DAY BASIC MICROBIOLOGY & PARASITOLOGY EXAMINATION 08.00-09.00 09.00-10.00 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 12.30-14.00 10.00-11.30 14.00-15.00 15.00-16.00 08.00-09.00 09.00-10.00 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 12.30-14.00 10.00-11.30 14.00-15.00 15.00-16.00 08.00-16.00 08.00-16.00 08.00-09.00 09.30-10.00 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 12.30-14.00 10.00-11.30 Lecture 33 Host response to infection (viral, bacterial, fungal, parasite) Lecture Individual learning Small group discussion Individual learning Plenary Lecture 34, 35, 36 Hematology & Immunology infection (dengue fever, dengue hemorrhagic fever, dengue shock syndrome) Lecture Individual learning Small group discussion Individual learning Plenary STUDENT PROJECT (ENGLISH CLASS) Lecture 37 Infection in pregnancy (TORCH in pregnancy) Udayana University Faculty of Medicine, DME, 2016 Class room Prof. Dr. dr. Tuti Parwati Merati, SpPD, KPTI Disc. Room Facilitator Class room Prof. Dr. dr. Tuti Parwati Merati, SpPD, KPTI dr Dewi Dian Sukmawati, SpPD Class room Disc. Room Facilitator Class room dr Dewi Dian Sukmawati, SpPD Evaluator & Fasilitator Teather room Lecture Class room DR Dr IB Fajar Manuaba, SpOG Individual learning Small group discussion Individual Disc. Room Facilitator 11 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases DAY/ DATE 20 Friday, Oct 7th 2016 21 Monday, Oct 10th 2016 22 Tuesday, Oct 11st 2016 23 Wednesday, Oct 12nd 2016 Time Regular Class English Class Topic Learning situation Place learning Plenary Class room DR Dr IB Fajar Manuaba, SpOG dr Susila Utama, SpPDKPTI dr Agus Somia, SpPD-KPTI 14.00-15.00 15.00-16.00 08.00-08.30 09.00-09.30 Lecture 38 Malaria Lecture Class room 08.30-09.00 09.30-10.00 Lecture 39 Leptospirosis Lecture Class room 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 12.30-14.00 10.00-11.30 14.00-14.30 15.00-15.30 Individual learning Small group discussion Individual learning Plenary 14.30-15.00 15.30-16.00 Plenary Class room 08.00-09.00 09.00-10,00 Lecture Class room 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 12.30-14.00 10.00-11.30 14.00-15.00 15.00-16.00 08.00-09.00 09.30-10.00 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 12.30-14.00 10.00-11.30 14.00-15.00 15.00-16.00 08.00-09.00 09.00-10.00 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 12.30-14.00 10.00-11.30 14.00-15.00 15.00-16.00 Lecture 40 Skin infection Individual learning Small group discussion Individual learning Plenary Lecture 41 Central nervous system infection (meningitis, encephalitis) Lecture Individual learning Small group discussion Individual learning Plenary Lecture 42 Child Immunization Udayana University Faculty of Medicine, DME, 2016 PIC Disc. Room Facilitator Class room dr Susila Utama, SpPDKPTI dr Agus Somia, SpPD-KPTI dr Ratih Karna, SpKK Disc. Room Facilitator Class room Class room dr Ratih Karna, SpKK Prof DR Dr Raka Sudewi, SpS(K) Disc. Room Facilitator Class room Prof DR Dr Raka Sudewi, SpS(K) dr W. Gustawan, SpA Lecture Class room Individual learning Small group discussion Individual learning Plenary Class room Facilitator Class room dr W. 12 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases DAY/ DATE 24 Thursday, Oct 13rd 2016 25 Friday, Oct 14th 2016 26 Monday, Oct 17th 2016 Time Regular Class English Class Topic Learning situation Place PIC Session Lecture Class room Gustawan, SpA dr Agus Somia, SpPD-KPTI Lecture Class room dr Yuli Gayatri, SpPD 08.00-08.30 09.00-10.00 Lecture 43 Thypoid fever 08.30-09.00 09.30-10.00 Lecture 44 Acute gastroenteritis 09.00-10.30 12.00-13.30 Individual learning 10.30-12.00 13.30-15.00 Disc. Room Facilitator 12.30-14.00 10.00-11.30 Small group discussion Individual learning 14.00-14.30 15.00-15.30 Class room 14.30-15.00 15.30-16.00 08.00-08.30 09.00-09.30 Lecture 45 Urinary Tract Infection (acute pyelonephritis, lower urinary tract infection) Plenary Session Plenary Session Lecture dr Agus Somia, SpPD-KPTI dr Yuli Gayatri, SpPD DR Dr Wayan Sudhana, SPPD-KGH 08.30-09.00 09.30-10.00 Lecture 46 Lower respiratory tract infection (pneumonia, acute bronchitis) Lecture Class room dr. Made Bagiada, SpPDKP 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 Disc. Room Facilitaor 12.30-14.00 10.00-11.30 Individual learning 14.00-14.30 15.00-15.30 Plenary Session Class room 14.00-14.30 15.00-15.30 Plenary Session Class room 08.00-08.30 09.00-09.30 Lecture Class room 08.30-09.00 09.30-10.00 Lecture Class room DR Dr Wayan Sudhana, SPPD-KGH dr. Made Bagiada, SpPDKP dr Yuli Gayatri, SpPD dr Dewi Dian Sukmawati, SpPD 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 12.30-14.00 10.00-11.30 14.00-14.30 15.00-15.30 Individual learning Small group discussion Lecture 47 Toxoplasmosis Lecture 48 Filariasis Udayana University Faculty of Medicine, DME, 2016 Individual learning Small group discussion Individual learning Plenary Session Class room Class room Disc. Room Facilitaor Class room dr Yuli Gayatri, SpPD 13 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases DAY/ DATE 27 Tuesday, Oct 18th 2016 28 Wednesday Oct 19th 2016 29 Thursday, Oct 20th 2016 30 Friday, Oct 21st Time Topic Learning situation Place PIC Plenary Session Class room Lecture Class room dr Dewi Dian Sukmawati, SpPD Prof DR Dr Tuti Parwati, SpPDKPTI Regular Class English Class 14.30-15.00 15.30-16.00 08.00-09.00 09.00-10.00 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 12.30-14.00 10.00-11.30 14.00-15.00 15.00-16.00 08.00-09.00 09.00-10.00 09.00-10.30 12.00-13.30 10.30-12.00 13.30-15.00 12.30-14.00 10.00-11.30 Individual learning 14.00-15.00 15.00-16.00 08.00-08.30 09.00-09.30 Lecture 52 Parotitis 08.30-09.00 09.30-10.00 Lecture 53 Bacteremia, Sepsis 09.00-10.30 12.00-13.30 Individual learning 10.30-12.00 13.30-15.00 Small group discussion 12.30-14.00 10.00-11.30 Individual learning 14.00-14.30 15.00-15.30 14.30-15.00 15.30-16.00 08.00-08.30 09.00-09.30 Lecture 49 HIV infection (pathogenesis & opportunistic infection) Individual learning Small group discussion Individual learning Plenary Session Lecture 50, 51 Avian influenza, SARS Lecture Individual learning Small group discussion Lecture 54 Rabies Udayana University Faculty of Medicine, DME, 2016 Disc. Room Facilitaor Class room Prof DR Dr Tuti Parwati, SpPDKPTI dr Agus Somia, SpPD-KPTI Class room Disc. Room Facilitaor Plenary Session Lecture Class room Lecture Class room dr Agus Somia, SpPD-KPTI dr Dewi Dian Sukmawati, SpPD dr Susila Utama, SpPDKPTI Class room Disc. Room Facilitaor Plenary Session Class room Plenary Session Class room Lecture Class room dr Dewi Dian Sukmawati, SpPD dr Susila Utama, SpPDKPTI dr Susila Utama, SpPDKPTI 14 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases DAY/ DATE 2016 31 Monday, Oct 24th 2016 32 Tuesday, Oct 25th 2016 33 Wednesday, Oct 26th 2016 34 Thursday, Oct 27th 2016 Friday, Oct 28th 2016 Monday, Oct 31st 2016 Time Learning situation Topic Place PIC Regular Class English Class 08.00-09.00 09.30-10.00 09.00-10.30 12.00-13.30 Individual learning 10.30-12.00 13.30-15.00 Small group discussion 12.30-14.00 10.00-11.30 Individual learning 14.00-14.30 15.00-15.30 14.30-15.00 15.30-16.00 08.00-15.00 09.00-16.00 Laboratory Practice 1: Gram Stain Laboratory Microbiology Team 08.00-15.00 09.00-16.00 Laboratory Practice 2: ZN stain Laboratory Microbiology Team 08.00-15.00 09.00-16.00 Laboratory Practice 3: Fecal examination Parasitology Team 08.00-15.00 09.00-16.00 Laboratory Practice 4: Parasit identification Parasitology Team Lecture 55 Tetanus Lecture Class room dr Yuli Gayatri, SpPD Disc. Room Facilitaor Plenary Session Class room Plenary Session Class room dr Susila Utama, SpPDKPTI dr Yuli Gayatri, SpPD SILENT DAY INFECTION & INFECTIOUS DISEASES EXAMINATION Udayana University Faculty of Medicine, DME, 2016 15 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases MEETING OF STUDENT REPRESENTATIVES In the middle of block period, a meeting is designed among the student representatives of every small group discussion, facilitators and source person of the block. The meeting discuss about the ongoing teaching and learning process, quality of facilitator and lectures as a feedback to improve the next process. MEETING OF THE FACILITATORS All facilitators are invited to discuss all block activities with block contributors 1 week after meeting of student representatives. ASSESSMENT METHOD 1. Assessment will be held twice, for basic microbiology & parasitology and infection & infectious diseases. Final mark is combination beteween this mark. The time provision is 100 minutes. The number of MCQ is 100 with passing point 70. 2. Assessment in this block consists of: SGD : 5% Student Project (Paper) : 10% Exam (basic & clinical) : 85% Udayana University Faculty of Medicine, DME, 2016 16 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases STUDENT PROJECT Regulation: TITLE Name: NIM: Faculty of Medicine, Udayana University 2016 1. 2. 3. 4. 5. Introduction (Pendahuluan) Content (Isi sesuai dengan judul paper) Summary (Ringkasan) References (Daftar pustaka): Vancouver style Pages: 6-10, Spasi: 1.5, Time New Roman:12 TOPIC Regular Class (Class A) GROUP DATE & TIME TITLE 6 Tuesday, Cerebral abses Sept 20th 2016, 08.30-09.00 09.00-09.30 Cerebral toxoplasmosis 09.30-10.00 Multi drug resisten (MDR) TB 10.00-10.30 Spondilitis TB 10.30-11.00 Acute infection pancreatitis 11.00-11.30 Pes 7 11.30-12.30 12.30-13.00 BREAK Leishmaniasis 8 13.00-13.30 Tripanosomiasis 9 13.30-14.00 10 14.00-14.30 Cytomegalovirus infection Squamous cell carcinoma (associated with HPV infection) 1 2 3 4 5 Udayana University Faculty of Medicine, DME, 2016 PEMBIMBING/ FASILITATOR dr. Ni Made Susilawathi, Sp.S dr. Ketut Agus Somia, Sp.PD-KPTI dr. Tjok Istri Anom Saturti, Sp.PD dr. Putu Sudira, Sp.S dr. Agus Roy Rusly HH, Sp.BE-RE dr. IA Dewi Wiryanthini, M.Biomed dr. IN Gede Wardana, M. Biomed Prof. Dr. dr. I Putu Adiatmika, M.Ked dr. I Wayan Juli Sumadi, Sp.PA dr. IA Kusuma Wardani, Sp.KJ, MARS EVALUATOR Prof DR Dr Raka Sudewi, SpS(K) dr. Made Bagiada, SpPDKP dr. Agus Somia, SpPD-KPTI Dr. dr. Made Sudarmaja, M.Kes dr. NN Dwi Fatmawati, Sp.MK, Ph.D 17 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases TOPIC English Class (Class B) GROUP DATE & TIME TITLE 2 Wednesday, Oct 5th 2016, 08.30-09.00 09.00-09.30 3 09.30-10.00 4 10.00-10.30 5 10.30-11.00 6 11.00-11.30 Carcinoma servik (associated with HPV infection) Penyakit jantung rematik Endoftalmitis 7 11.30-12.30 12.30-13.00 BREAK Hepatitis C 8 13.00-13.30 Abses payudara 9 13.30-14.00 Epididimitis 10 14.00-14.30 Herpes genital tipe 2 1 Nasopharyngeal carcinoma (associated with EBV infection) Hairy leukoplakia (associated with EBV infection) Korioretinitis Udayana University Faculty of Medicine, DME, 2016 PEMBIMBING/ FASILITATOR dr. Komang Andi Dwi Saputra, Sp.THT-KL dr. Henky, Sp.F, M.Beth EVALUATOR dr. Made Agus Hendrayana, M.Ked dr. I Wayan Niryana, Sp.BS, M.Kes dr. Ni Nyoman Metriani Nesa, Sp.A, M.Sc Dr. dr. BK Satriyasa, M.Repro Dr. dr. GN Indraguna P dr. Kadek Swastika, M.Kes dr. IA Rangga W, Sp.JP, FIHA, M.Biomed dr. I Wayan Sugiritama, M.Kes dr. Tjahya Aryasa EM, Sp.An Desak Ernawati, S.Si PGPharm, M.Pharm,Ph.D dr. Ni Made Dewi Dian Sukmawati, Sp.PD dr W. Gustawan, SpA dr. Ratih Karna, SpKK 18 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases LEARNING PROGRAM LECTURE 1 INTRODUCTION OF BLOCK BASIC INFECTION AND INFECTIOUS DISEASES Prof. Dr. dr. Tuti Parwati Merati, SpPD, KPTI Abstract Infections and infectious diseases are a great burden on many societies, including Indonesia. To reduce that burden an integrated approach is required, combining health promotion, disease prevention and patient treatment. The prerequisite for success in this fight is the participation of all health care professionals. Should know and understand terminology commonly use in the context of infectious disease. Infectious diseases are disorders or diseases caused by organisms — such as bacteria, viruses, fungi or parasites. Many organisms live in and on our bodies. They're normally harmless or even helpful, which we called them normal flora; but under certain conditions, some organisms may cause disease. This organisms called as pathogen as they can produced pathology to the body. Infectious diseases are one of the leading causes of death worldwide. Infectious diseases can be spread directly or indirectly . Some infectious diseases can be passed from person to person. Some are transmitted by bites from insects or animals. And others are acquired by ingesting contaminated food or water or being exposed to organisms in the environment. Many infectious diseases become difficult to control if the infectious agents evolve resistance to commonly used drugs: For example, bacteria can accumulate mutations in their DNA or acquire new genes that allow them to survive contact with antibiotic drugs that would normally kill them. Signs and symptoms vary depending on the organism causing the infection, but often include fever and fatigue. Mild infections may respond to rest and home remedies, while some life-threatening infections may require hospitalization. Many infectious diseases, such as measles and chickenpox, can be prevented by vaccines but many other still do not have vaccine available. Other prevention mean such as frequent and thorough hand-washing helps protect from most infectious diseases. Symptoms Each infectious disease has its own specific signs and symptoms. General signs and symptoms common to a number of infectious diseases include: fever, fatigue, muscle aches, coughing and diarrhea Transmission: an infection can be spread through direct and indirect contact Direct contact An easy way to catch most infectious diseases is by coming in contact with a person or animal who has the infection. Three ways infectious diseases can be spread through direct contact are: Person to person. A common way for infectious diseases to spread is through the direct transfer of bacteria, viruses or other germs from one person to another. This can occur when an individual with the bacterium or virus touches, kisses, or coughs or sneezes on someone who isn't infected. These germs can also spread through the exchange of body fluids from sexual contact. The person who passes the germ may have no symptoms of the disease, but may simply be a carrier. Udayana University Faculty of Medicine, DME, 2016 19 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases Animal to person. Being bitten or scratched by an infected animal — even a pet — can make you sick and, in extreme circumstances, can be fatal. Handling animal waste can be hazardous, too. For example, you can acquire a toxoplasmosis infection by scooping your cat's litter box. Mother to unborn baby. A pregnant woman may pass germs that cause infectious diseases to her unborn baby. Some germs can pass through the placenta. Germs in the vagina can be transmitted to the baby during birth. Indirect contact Touching : Disease-causing organisms also can be passed by indirect contact. Many germs can linger on an inanimate object, such as a tabletop, doorknob or faucet handle. When you touch a doorknob handled by someone ill with the flu or a cold, for example, you can pick up the germs he or she left behind. If you then touch your eyes, mouth or nose before washing your hands, you may become infected. Vectors/insect bites - Some germs rely on insect carriers — such as mosquitoes, fleas, lice or ticks — to move from host to host. These carriers are known as vectors. Mosquitoes can carry the malaria parasite or West Nile virus, and deer ticks may carry the bacterium that causes Lyme disease. Food/water contamination : disease-causing germs can infect you is through contaminated food and water. This mechanism of transmission allows germs to be spread to many people through a single source. E. coli, for example, is a bacterium present in or on certain foods — such as undercooked hamburger or unpasteurized fruit juice. Risk factors Anyone can catch infectious diseases easier than other people because the body immune system is not work well. This may occur if there are primary or secondary immune deficiency , such as : Taking steroids or other medications that suppress immune system, such as anti-rejection drugs for a transplanted organ, certain types of cancer or other disorders that affect the immune system, infection by HIV or AIDS. In addition, certain other medical conditions may predispose you to infection, including implanted medical devices, malnutrition and extremes of age, among others. Complications Most infectious diseases have only minor complications. But some infections — such as pneumonia, AIDS and meningitis — can become life-threatening. A few types of infections have been linked to a long-term increased risk of cancer: hepatitis B and C have been linked to liver cancer, human papillomavirus is linked to cervical cancer, Helicobacter pylori is linked to stomach cancer and peptic ulcers and In addition, some infectious diseases may become silent, only to appear again in the future — sometimes even decades later. For example, someone who's had a chickenpox infection may develop shingles much later in life. Diagnosis Diagnosis can be made with clinical symptoms and signs. Because many of infectious disease have a very similar symptoms and signs, usually laboratory or imaging test would be needed to confirmed the diagnosis Laboratory tests Many infectious diseases have similar signs and symptoms. Samples of body fluids can sometimes reveal evidence of the particular microbe that's causing illness. Samples can Udayana University Faculty of Medicine, DME, 2016 20 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases get from blood, urine, throat swabs, stool sample, spinal tap (lumbar puncture). A technician obtains a sample with a standard procedure from each. Imaging scans Imaging procedures — such as X-rays, computerized tomography and magnetic resonance imaging — can help pinpoint diagnoses and rule out other conditions that may be causing the symptoms. Biopsies During a biopsy, a tiny sample of tissue is taken from an internal organ for testing. For example, a biopsy of lung tissue can be checked for a variety of fungi that can cause a type of pneumonia. Treatment Knowing what type of germ is causing the illness makes it easier to choose appropriate treatment such as : antibiotics, anti viral, anti fungal, and anti-parasitics. However, the use of those agents should be use appropriately. The overuse of antibiotics has resulted in several types of bacteria developing resistance to one or more varieties of antibiotics. This makes these bacteria much more difficult to treat As an alternative medicine, a number of products have been purported to help fend off common illnesses, such as the cold or flu. Cranberry, echinacea, garlic, ginseng, vitamin C, D and zinc are among other.. While some of these substances have appeared promising in early trials, follow-up studies may have had negative or inconclusive results. More research needs to be done. Prevention Infectious diseases can be prevented by vaccines but many other still do not have vaccine available. Prevention to infectious disease transmission with no vaccine available should use another approach. Personal protected equipment such as gown, masker, google, gloves, and shoes boot. Infectious disease transmitted by vectors should avoid to being bitten by mosquitoes or other insects may be useful, such as wearing long sleeve shirt, and putting mosquitos repellent. Other prevention means such as frequent and thorough hand-washing helps protect from most infectious diseases. Learning tasks: 1. How do we know that a patient in our hospital is suffering from a kind of infectious disease? 2. How he or she can get it? 3. What prevention do we need to do to avoid of getting any infectious diseases? Self assessment: 1. Describe all common terminology use in the context of infectious diseases. 2. Describe general clinical manifestation of infectious diseases. 3. Describe pathogenesis of general symptoms of infectious disease. Udayana University Faculty of Medicine, DME, 2016 21 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases LECTURE 2 GENERAL PARASITOLOGY Dr. dr. Made Sudarmaja, M. Kes Abstract Parasitology: The study of PARASITES and their relationships to their HOSTS. Parasite : A living organism which receives nourishment and shelter from another organism where it lives. Host : An organism which harbours the parasites. Parasite depend on its location of infection divided into ectoparasites and endoparasites. Some term of parasites : facultative parasites, obligate parasites, incidental parasites, temporary parasites, permanent parasites, pathogen parasites and pseudoparasite. Host divided into definitive host and intermediate host. The study of Parasitology consist several aspect such as : epidemiology, habitat, morphology, life cycle, pathogenic effect, sign & symptom, diagnosis & laboratory diagnosis, treatment and prophylaxis. In The Indonesian Standard Competency of Doctor (SKDI = Standar Kompetensi Dokter Indonesia) shown that several diseases that caused by parasites must be competence by general practioner such as : Malaria, Filariasis, Toxoplasmosis, mikosis, Hookworm infection, Amoebiasis, Ascariasis, Trichuriasis, Enterobiasis, Strongyloidiasis, Schistosomiasis, Taeniasis, Scabies, Pediculosis capitis and Pthiriasis pubis Learning task: 1. Explain differentiation between Hospes definitive and Hospes intermediate and give example hospes definitive and hospes intermediate! 2. Mention and explain the infective stage of several parasites that caused diseases in human 3. The preventive and control the parasites disesase must be based on life cycle of parasites. Why? Self-Assessment 1. Amoebic dysentri caused by: A. Ascaris lumbricoides B. Necator americanus C. Trichuris trichiura D. Brugia malayi E. Entamoeba histolytica 2. Tapeworm that transmitted with pork A. Taenia saginata B. Taenia solium C. Hymenolepis nana D. Hymenolepis diminuta 3. Nematode that include of soil transmitted helminthes: A. Enterobius vermicularis B. Taenia saginata C. Trichinella spiralis D. Brugia malayi E. Trichuris trichiura Udayana University Faculty of Medicine, DME, 2016 22 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases LECTURE 3 INTRODUCTION OF MICROBIOLOGY Dr. dr. I Dewa Made Sukrama, M. Si, Sp.MK ABSTRACT The discipline of bacteriology evolved from the need of physicians to test and apply the germ theory of disease and from economic concerns relating to the spoilage of foods and wine. The initial advances in pathogenic bacteriology were derived from the identification and characterization of bacteria associated with specific diseases. During this period, great emphasis was placed on applying Koch's postulates to test proposed cause-and-effect relationships between bacteria and specific diseases. Today, most bacterial diseases of humans and their etiologic agents have been identified, although important variants continue to evolve and sometimes emerge, e.g., Legionnaire's Disease, tuberculosis and toxic shock syndrome. Major advances in bacteriology over the last century resulted in the development of many effective vaccines (e.g., pneumococcal polysaccharide vaccine, diphtheria toxoid, and tetanus toxoid) as well as of other vaccines (e.g., cholera, typhoid, and plague vaccines) that are less effective or have side effects. Another major advance was the discovery of antibiotics. These antimicrobial substances have not eradicated bacterial diseases, but they are powerful therapeutic tools. Their efficacy is reduced by the emergence of antibiotic resistant bacteria (now an important medical management problem) In reality, improvements in sanitation and water purification have a greater effect on the incidence of bacterial infections in a community than does the availability of antibiotics or bacterial vaccines. Nevertheless, many and serious bacterial diseases remain. LEARNING TASK: 1. Define and apply major taxonomic group when classifying microorganisms (bacteria, fungi, parasites, and viruses) 2. Relate microbial cell structure and processes to growth, disease, survival, or other relevant phenotypes. 3. Be able to describe the principle of Koch’s postulate. LECTURE 4 PATHOGENESIS OF BACTERIAL INFECTION dr. Made Agus Hendrayana, M. Ked ABSTRACT Pathogenesis is a multi-factorial process which depends on the immune status of the host, the nature of the species or strain (virulence factors) and the number of organisms in the initial exposure. A limited number of bacterial species are responsible for the majority of infectious diseases in healthy individuals. Due to the success of vaccination, antibiotics, and effective public health measures, until recently, epidemics were felt to be a thing of the past. Due to the development of antibiotic resistant organisms, this situation is changing rapidly. All humans are infected with bacteria (the normal flora) living on their external surfaces Udayana University Faculty of Medicine, DME, 2016 23 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases (including the skin, gut and lungs). We are constantly also exposed to bacteria (including air, water, soil and food). Normally due to our host defenses most of these bacteria are harmless. The pathogenesis of bacterial infection includes initiation of the infectious process and the mechanisms that lead to the development of signs and symptoms of disease. The biochemical, structural, and genetic factors that play important roles in bacterial pathogenesis are introduced in this chapter and may be revisited in the organism-specific sections. Characteristics of bacteria that are pathogens include transmissibility, adherence to host cells, persistence, invasion of host cells and tissues, toxigenicity, and the ability to evade or survive the host's immune system. Resistance to antimicrobials and disinfectants can also contribute to virulence, or an organism's capacity to cause disease. Many infections caused by bacteria that are com-monly considered to be pathogens are inapparent or asymptomatic. Disease occurs if the bacteria or immunologic reactions to their presence cause sufficient harm to the person. Learning Task Case: A 15 years old female, a student at Junior High School, come to general practician complained that she has fever since 6 days. The fever is intermitten, commonly arise when aftenoon till night, but back to normal in the morning. She feels slightly discomfort at the abdominal. She also complained that not defecated since 4 days. Other physical examination results are normal. The practician ask for laboratory examination and culture. After few days, the laboratory analysis shown that she has typoid fever. The culture shown colonies of Salmonella typhi bacteria and significant as agent of infection. 1. What are Salmonella typhi’s virulence factors that can cause infection? 2. Explain the microbial virulence factors that you know! 3. What are Salmonella typhi ’s virulence factors that can cause infection? 4. Explain the pathogenesis how Salmonella typhi can infect the human (from transmission until infection and cause the disease)! 5. Whether the virulence factors of each microbial is the same? Why? 6. When any bacteria called as colonization bacteria? 7. Explain the differentiation between true pathogen and opportunistic pathogen! 8. Explain the differentiation between exotoxins and endotoxin ! 9. Describe how several pathogens are able to survive inside the macrophages ! 10. Explain the routes of transmission that you know and give examples of each ! 11. Explain why are important to know about the bacteria virulence factors Self Assessment 1. Explain the meaning of this term above: A. Contamination B. Colonization C. Invasion D. Infection E. Pathogen F. Carrier G. Nonpathogenic H. Opportunistic pathogen I. Pathogenicity: Udayana University Faculty of Medicine, DME, 2016 24 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases J. Toxigenicity: K. Virulence: L. Symbiosis M. Commensalism N. Parasitism O. Zoonoses 2. Give examples of attachment mechanism ! Reff : Jawetz, Melnick, Adelberg. 2013 Chapter 9. Pathogenesis of Bacterial Infection in Medical Microbiology, 26th Edition by Vishal . The McGraw-Hill Companies. Lange Microbiology. LECTURE 5 DIAGNOSIS OF MALARIA Dr. dr. Made Sudarmaja, M.Kes Abstract Malaria remains a global health problem and also in Indonesia and can cause death, especially in high-risk such as infants, toddlers and pregnant women. Malaria Diagnosis is made by anamnesis, physical examination and laboratory tests. To get a definite diagnosis of malaria should be performed laboratory tests to find the malaria parasite in the blood. Examination and detection of the parasite causing-malaria in blood can be done by: a microscopic examination (blood smear), Rapid Diagnostic Test (RDT) and examination by PCR. Blood smear using microscopic examination is the gold standard for the diagnosis of malaria. Examination of blood smear can be developed thick and thin blood smear. Examination of blood smear aims to found the Plasmodium (malaria parasite), plasmodium determine species and stage and parasite density. Examination using RDT aims to detect the presence of malaria parasite antigens using immunochromatography. PCR can only be done in health facilities that have the equipment for inspection biomoleculer. Learning task 1. How to distinguish species of malaria by peripheral blood smear examination? LECTURE 6 DIAGNOSIS OF FILARIASIS Dr. dr. Made Sudarmaja, M.Kes Abstract The infection of filariasis affects 120 million people living in 73 countries, leaving some 40 million profoundly disfigured and incapacitated.The diagnosis of filariasis enforced through anamnesis, physical examination and investigation of the examination of blood smears for the presence of microfilaria in the peripheral blood. The microfilariae that cause lymphatic Udayana University Faculty of Medicine, DME, 2016 25 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases filariasis circulate in the blood at night (called nocturnal periodicity). Blood collection should be done at night to coincide with the appearance of the microfilariae, and a thick smear should be made and stained with Giemsa or hematoxylin and eosin. Learning task 1. How to differentiated species caused filariasis in the examination of blood smears? Self Assessment 1. Sexual reproduction of P vivax take place in: A. Human gut B. Red blood cells C. Mosquito D. Liver cell E. Human Leucocyts 2. The species of plasmodium is characterized by cressent shaped gametocytes and multiple ring forms whitin RBC: A. P vivax B. P falciparum C. P ovale D. P malariae E. P knowlesi 3. The dormant parasite forms found in patient with vivax malaria are called: A. Thropozoites B. Sporozoites C. Hypnozoites D. Gametocytes E. Merozoites 4. Sheated microfilaria, described as having two discrete nuclei in the tip of a pointed tail A. W bancrofti B. B malayi C. Loa loa D. Onchocerca volvulus LECTURE 7, 8 TOXOPLASMOSIS & AMOEBIASIS dr. Luh Ariwati Entamoeba histolytica is a protozoan parasite responsible for a disease called amoebiasis. It occurs usually in the large intestine and causes internal inflammation as its name suggests (histo = tissue, lytic = destroying). Protozoa are unicellular organisms that have trophozoite form with one or more nuclei containing nucleoli or karyosome and bounded by a nuclear membrane and the usual eukaryotic cytoplasmic organelles including mitochondria ribosomes and endoplasmic reticulum. Trophozoite have a cell membrane but not cell wall. Most intestinal Protozoa also develop cyst that are more resistant than the fragile trophozoite to drying, cold or other environmental stresses. Udayana University Faculty of Medicine, DME, 2016 26 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases Amoebiasis is diagnosed under a microscope by finding cysts and (rarely trophozoites) from a stool sample. The results are usually said to be negative, if Entamoeba histolytica is not found in three different stool samples. But it still does not necessarily mean that you are not infected because the microscopic parasite is hard to find and it might not be present the particular samples. A blood test might also be available but is only recommended, if your health care provider believes that the infection could have spread to other parts of the body. Trophozoites can be identified under a microscope from biopsy samples taken during colonoscopy or surgery. Toxoplasmosis well known as parasitic disease and have great impact due to their worldwide distribution. Toxoplasma is caused by a coccidian parasite, Toxoplasma gondii. It has a worldwide distribution and shows a broad host range from warm blooded animals to birds and reptiles. Man acquires the infection indirectly by ingesting oocysts from contaminated environments, by consuming Toxoplasma cysts from tissues of other intermediate hosts such as cow, goat, chicken, duck, rabbit, by blood transfusion or transplantation, or directly by transplacental infection Human infection is generally asimptomatic and self limited except in immunocompromised host, infection can disseminated and fatal. The prevalence of antibody to toxoplasma in human and animal ranged from 2% to 75% in Southeast Asian Countries. Cats are the definitive host of T. gondii; they are the only animals that pass oocysts in their feces . Learning Tasks A previously healthy 28-year old man, who had recently returned from a trip to Lombok, was seen by his family physician for crampy abdominal pain, malaise, slight fever and bloody, mucoid diarrhea. Liquid stool specimens were collected and submitted for culture for enteric bacterial pathogens as well as parasites. Stool cultures were negative for bacterial pathogens, examination for ova and parasites was positive for motile trophozoites in the saline wet amount, and ameboid trophozoites with finely granular cytoplasm and ingested red blood cells in the permanent trichrome stain. a. Describe the life cycle of parasites above ! b. Explain the pathogenesis of parasite above! c. Describe infective stages of parasite above! 1. Describe the life cycle of Toxoplasma gondii 2. Explain transmission of Toxoplasma gondii infection 3. Explain why toxoplasma infection became latency LECTURE 9 SYSTEMIC FUNGAL INFECTION dr. Luh Ariwati Humans have good barriers against fungal infection such as intact skin, mucosal surfaces, saliva, normal bacterial flora etc. Healthy, immunocompetent people have a high innate resistant to fungi even though they are constantly exposed to the propagules of fungi. Udayana University Faculty of Medicine, DME, 2016 27 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases Infections and diseases occur when there are disruptions in the protection barrier of skin and mucus membrane or defect in immunity system. The characteristic of fungal pathogens categorized into groups according to tissue that they colonize: superficial, cutaneous, subcutaneous and systemic mycosis. Fungal infections that occur only because of compromising situations are categorized as opportunistic mycosis. Systemic Fungal infections have become increasingly frequent especially in immune compromised host such as AIDS, cancer patients, organ transplantation , and also as a consequent of the availability of advanced medical technology which allow to do more invasive treatment using more invasive instruments. The aetiology are : Predominant fungi : Candida (C): such as C. Albicans, C. glabrata, C. tropicalis and C.parapsilopsis, Aspergillus spp.and Cryptococcus spp., Emerging fungi : Fusarium spp., and Rhizopus spp. and Endemic fungi : Histoplasma capsulatum, Blastomyces dermatitidis and Coccidioides immitis There is no specific sign and symptoms of systemic fungal infection. That is why suspected clinical diagnosis of systemic fungal infection is frequently late. Its resemble bacterial infections, such as severe sepsis, septic shock and multi organ failure. Alertness to this infection will comes late though sign and symptoms appear early. In many cases the diagnosis was done per exlusionem. Diagnosis should be considered in patient with risk factors has the signs of systemic infection despite adequate antibiotics. Learning Tasks: 1. Describe the cause and the risk factors of Systemic Fungal Infection 2. Describe the Laboratory diagnosis of candidiasis 3. Describe the morphologic different between Candida and Cryptococcus sp in direct microscopic examination LECTURE 10, 11 ASCARIASIS & TRICHURIASIS dr. Luh Ariwati Infections with soil-transmitted helminths (STHs: Ascaris, Trichuris, Hookworm and Strongiloides), which are intestinal worms transmitted through contaminated soil, are the most common infections worldwide. Globally, more than 1 billion people are infected with one or more STHs, mainly in areas with warm and moist climates where sanitation and hygiene are poor. Infection with STH contributes to anemia, vitamin A deficiency, malnutrition and impaired growth, delayed development, and intestinal blockages. Ascariasis is a Soil-transmitted helminthiasis (STH) infection caused by the roundworm Ascaris lumbricoides (A. lumbricoides). Ascariasis, one of the most common STH infections, affects an estimated 1 billion people worldwide. About half of the populations in tropical and subtropical areas are infected with this parasite, which causes an estimated 20,000 deaths each year. While mild cases of ascariasis often show no symptoms, heavy infections can cause intestinal blockage and impair growth in children. Ascariasis infection is highly prevalent and geographically widespread. Many factors, including the large number of eggs produced by a female worm, the properties of the eggs, Udayana University Faculty of Medicine, DME, 2016 28 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases environmental conditions, and poor socioeconomic settings facilitate the spread of the parasite and thus determine the geographic distribution of the disease. Children, especially those suffering from malnutrition, are infected more often than adults, with the most common age group being 3 to 8 year olds. Children often become infected by playing in contaminated soil, but eating uncooked food grown in contaminated soil or irrigated with inadequately treated wastewater is another frequent avenue of infection. Whipworm (Trichuris trichiura) is the third most common roundworm found in humans. The name "whipworm" refers to the shape of the worm; the worms look like whips with wider "handles" at the posterior end. Globally, nearly 800 million people are infected with whipworms, which are highly prevalent in children. Heavy infections could lead to shortterm symptoms such as diarrhea and anemia and longer-term symptoms such as growth retardation and impaired cognitive development. Coinfection of whipworm with Giardia, Entamoeba histolytica, Ascaris lumbricoides, and hookworm is common. Whipworm infection, known as trichuriasis, is prevalent in both temperate and tropical zones of the world. However, infections follow a clustered distribution and are more frequently found in areas with tropical weather and poor sanitation practices. Whipworm infection occurs through ingestion of whipworm eggs, which can be found in fecally contaminated dry goods, such as beans, rice, and various grains, and in crops grown in soil fertilized with sewage. Humans are infected when such produce is consumed raw or food is contaminated by handlers. Learning Tasks: 1. Differentiate the morphological characteristics of A.lumbricoides and T. trichiura 2. Describe their life cycles and identify each of their infective stages 3. Describe their pathogenesis and clinical manifestations 4. Identify their stages of development which are useful from the viewpoint of diagnosis purpose and try to figure their morphological characteristics 5. Define their epidemiological standpoints and list the factors that are closely related to the transmission of the infections 6. Manage appropriately the diagnosis, treatment, and prevention measures. LECTURE 12, 13, 14 HOOKWORM INFECTION, STRONGYLOIDIASIS AND ENTEROBIASIS Dr. dr. Made Sudarmaja, M.Kes Abstract Hookworm infection is an infection by a parasitic blood sucking roundworm Ancylostoma duodenale and Necator americanus. Hookworm infection is a soil-transmitted helminthiasis and therefore classified as a neglected tropical diseases.These worms live in the small intestine of human. Hookworm infection affects more than half a billion people in the world. In developing countries, hookworm infection is rarely fatal, but anemia can be significant in a heavily infected individual. Ancylostomiasis is the disease caused when Ancylostomaduodenale hookworms, present in large numbers, produce an iron deficiency anemia by sucking blood from the host's intestinal walls.Diagnosis of Ancylostomiasis and Udayana University Faculty of Medicine, DME, 2016 29 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases Necatoriasisdepends on finding characteristic worm eggs on microscopic examination of the stools Strongyloidiasis is a human parasitic disease caused by Strongyloidesstercoralis. This intestinal worm can cause a number of symptoms in people, principally skin symptoms, abdominal pain, diarrhea and weight loss. In some people, particularly those who require corticosteroids or other immunosuppressive medication, Strongyloides can cause a hyperinfection syndrome that can lead to death if untreated. The diagnosis is made by blood and stool tests. The drug Ivermectin is widely used in the treatment of strongyloidiasis. Other drugs that are effective are albendazole and thiabendazole (25 mg/kg twice daily for 5 days—400 mg maximum (generally)). Enterobiasis is an infection caused by Enterobiusvermicularis. Enterobiusvermicularis (Oxyurisvermicularis) also called human pinworm habits in caecum or in large intestinal. Adult females has lenght 8 to 13 mm, adult male: 2 to 5 mm. The infective stage of this worm is embryonated egg. The infection will be occurs through 3 routes: Self-infection occurs by transferring infective eggs to the mouth with hands that have scratched the perianal area Person-to-person transmission can also occur through handling of contaminated clothes or bed linens. Enterobiasis may also be acquired through surfaces in the environment that are contaminated with pinworm eggs (e.g. , curtains, carpeting). Some small number of eggs may become airborne and inhaled. These would be swallowed and follow the same development as ingested eggs. Following ingestion of infective eggs, the larvae hatch in the small intestine Retroinfection, or the migration of newly hatched larvae from the anal skin back into the rectum, may occur but the frequency with which this happens is unknown. Diagnostic: found specific egg using perianal swab (under microscope examination) Learning task: 1. Please explain the life cycle of Hookworm, Strongyloides stercoralis and Enterobius vermicularis! 2. Describe the prevention based on the life cucle from hookworm infections, strongyloidiasis and enterobiasis! 3. Explain symptoms and sign of hookworm infections, strongyloidiasis and enterobiasis! Self Assessment: 1. The “scoth tape test” is used to diagnose infection with: A. Ancylostoma duodenale B. Strongyloides stercoralis C. Necator americanus D. Enterobius vermicularis 2. The parasite is capable of autoinfection with may leadto hyperinfection syndrome: A. Ancylostoma duodenale B. Strongyloides stercoralis C. Necator americanus D. Enterobius vermicularis 3. The eggs of this helmiths is planoconvex and contain tad pole like larva: A. Ancylostoma duodenale B. Strongyloides stercoralis Udayana University Faculty of Medicine, DME, 2016 30 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases C. Necator americanus D. Enterobius vermicularis LECTURE 15, 16 LARVA MIGRANS & PEDICULOSIS dr. Kadek Swastika, M.Kes Abstract Cutaneous larva migrans caused by the larvae of animal hookworms. Humans normally become infected with the hookworm larvae by walking barefoot on a beach, or by contact with soil that is contaminated with animal faeces Cutaneous larva migrans is most commonly found in tropical and subtropical geographic areas and the southwestern United States. It has become an endemic in the Caribbean, Central America, South America, Southeast Asia, and Africa. However, the ease and the increasing incidence of foreign travel by the world's population have no longer confined cutaneous larva migrans to these areas. Cutaneous larva migrans is caused by the larvae of animal hookworms, of which Ancylostoma braziliense is the species most frequently found in humans [2, 3]. These hookworms generally live in the intestines of domestic pets such as dogs and cats and shed their eggs via feces to soil (usually sandy areas of beaches or under houses). Humans are infected in tropical and subtropical areas of endemicity by contact with contaminated soil. The hookworm larva burrows through intact skin but remains confined to the upper dermis, since humans are incidental hostsCreeping eruption usually appears 1–5 days after skin penetration, but the incubation period may be ≥1 month. Typically, a serpiginous, erythematous track appears in the skin and is associated with intense itchiness and mild swelling. Usual locations are the foot and buttocks, although any skin surface coming in contact with contaminated soil can be affected. Pediculosis is an infestation of the hairy parts of the body or clothing with the eggs, larvae or adults of lice. Lice infestation remains a major problem throughout the world, making the diagnosis and treatment of louse infestation a common task in general medical practice. Lice on human comprice three types, namely the body louse (Pediculus humanus), the head louse (Pediculus capitis) and the pubic louse (Pthirus pubis). Head, body and pubic lice are blood-sucking ectoparasites that are species of Anoplura. They are usually transmitted directly, by person-to-person contact, but they may also be transmitted indirectly, via the clothing, towelling and bedding of infested persons. Infestations occur throughout the world, particularly where there is overcrowding. Poor hygiene tends to increase the incidence of body lice infestations. Head lice infestation is very common and is distributed worldwide. Preschool and elementary-age children, 3 to 11 years of age are infested most often. Females are infested more often than males, probably due to more frequent head to head contact. Body lice are also cosmopolitan but are less common and usually seen in settings of poverty, war, and homelessness.The majority of head lice infestations are asymptomatic. When symptoms are noted they may include a tickling feeling of something moving in the hair, itching, caused by an allergic reaction to louse saliva, and irritability. Secondary bacterial infection may be a complication. Body lice can serve as vectors for Rickettsia prowazekii (epidemic typhus), Bartonella quintana (trench fever), and Borrelia recurrentis (louse-borne relapsing fever). Udayana University Faculty of Medicine, DME, 2016 31 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases Learning task 1 A 10-year-old girl accompany by her family come to the health center complaining of itchy head. Itching is already being felt since one month ago. Patients living in the dorms, some of the children who lived there also had the same complaint. On physical examination was found in scalp hair looks dull and contain white objects. 1. What is the etiology of that case? 2. Describe the life cycle that species! 3. Describe the mode of transmission of that case! 4. How to manage that case? Please explain the treatment and prevention. Learning task 2 A man 30 years old came to the clinic with complaints of redness track appears in the skin of left foot since 3 days ago. These symptom associated with intense itchiness and mild swelling. Last week he went to beach and walking around without slippers. On local examination found erythematous track on left foot. 1. What is the diagnosis of that case? 2. What are the possibility agents cause that case? 3. Describe the mode of transmission of that case 4. How to manage that case? Please explain the treatment and prevention LECTURE 17, 18, 19 SCHISTOSOMIASIS, TAENIASIS, SISTISERKOSIS dr. Kadek Swastika, M.Kes Abstract Schistosomiasis is an acute and chronic disease caused by parasitic worms. Schistosomiasis is caused by digenetic blood trematodes. The three main species infecting humans are Schistosoma haematobium, S. japonicum, and S. mansoni. Estimates show that at least 258 million people required preventive treatment in 2014. Preventive treatment, which should be repeated over a number of years, will reduce and prevent morbidity. Transmission occurs when people suffering from schistosomiasis contaminate freshwater sources with their excreta containing parasite eggs which hatch in water. People become infected when larval forms of the parasite – released by freshwater snails – penetrate the skin during contact with infested water. In the body, the larvae develop into adult schistosomes. Adult worms live in the blood vessels where the females release eggs. Some of the eggs are passed out of the body in the faeces or urine to continue the parasite’s life-cycle. Others become trapped in body tissues, causing immune reactions and progressive damage to organs. Schistosomiasis is diagnosed through the detection of parasite eggs in stool or urine specimens. Antibodies and/or antigens detected in blood or urine samples are also indications of infection. The WHO strategy for schistosomiasis control focuses on reducing disease through periodic, targeted treatment with praziquantel through the large-scale treatment (preventive chemotherapy) of affected populations. The cestodes, or tapeworms, constitute a class of phylum Platyhelminthes. The adult tapeworms found in human all have a flat and ribbonlike body. Living worms are white or yellowish. The cestode body consists of an anterior attachment organ, or scolex, Udayana University Faculty of Medicine, DME, 2016 32 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases followed by a chain segments or proglottids also known as strobila. Three spesies of human Taenia are recognized : Taenia solium, Taenia saginata and Taenia asiatica. All three spesies are important public health problems in endemic areas as foodborne zoonoses. The beef tapeworm occurs wherever people eat cured or undercooked beef infected with taenia saginata, and the pork tapeworm occurs wherever people eat cured or undercooked pork infected with taenia solium.Cysticercosis is caused by the larval stage of tapeworm Taenia solium. Taenia solium is endemic in all area of world where pigs are raised under conditions in which they have access to human fecal material. Highly endemic area of Taeniasis/Cysticercosis are in Latin America, Eastern Europe, sub-Saharan Africa, India, also recognized in Indonesia, Southeast Asia, China, Korea. In Indonesia there are three endemic provinces for taeniasis/cysticercosis : Bali, Papua and North Sumatra. Others provinces also reported this cases such as East Nusa Tenggara, Lampung, North Sulawesi, Southeast Sulawesi, and West Kalimantan. Learning Task A man 47 years old came to Primary Health care with the complained discomfort on his stomach since one month ago and sometimes accompanied with diarrhea, No fever. He is a Balinese and work as a social worker. Physical examination found temperature 37,1 ° C, Blood pressure 120/80 mmHg. Stool examination found an oval egg size 35 µm, with radially striated brown sell and six hooked onchospere 1. What other information you need to complete the diagnosis? 2. What is the possibility diagnosis and how to manage this patient 3. What is additional examination you need to know the species? 4. On gravid proglotids found 11 uterine branch, Please Describe the life cycle of this species! 5. What is possibility complication caused by this spesies? And how it can be occur? LECTURE 20, 21 GRAM POSITIVE AND NEGATIVE BACTERIA dr. Made Agus Hendrayana, M. Ked ABSTRACT Danish scientist Hans Christian Gram devised a method to differentiate two types of bacteria based on the structural differences in their cell walls. In his test, bacteria that retain the crystal violet dye do so because of a thick layer of peptidoglycan and are called Gram-positive bacteria. In contrast, Gram-negative bacteria do not retain the violet dye and are colored red or pink. Compared with Gram-positive bacteria, Gram-negative bacteria are more resistant against antibodies because of their impenetrable cell wall. These bacteria have a wide variety of applications ranging from medical treatment to industrial use In a Gram stain test, bacteria are washed with a decolorizing solution after being dyed with crystal violet. On adding a counterstain such as safranin or fuchsine after washing, Gramnegative bacteria are stained red or pink while Gram-positive bacteria retain their crystal violet dye. This is due to the difference in the structure of their bacterial cell wall. Grampositive bacteria do not have an outer cell membrane found in Gram-negative bacteria. The Udayana University Faculty of Medicine, DME, 2016 33 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases cell wall of Gram-positive bacteria is high in peptidoglycan which is responsible for retaining the crystal violet dye. 90-95% of Gram negative bacteria are pathogenic. On the other hand, many Gram-positive bacteria are non-pathogenic. Not only do gram-negative bacteria tend to be harmful to humans, they are also more resistant to antibiotics. LEARNING TASK Case: A 25 years old male, collage student, come to clinic complained that there are infected wound on his right foot. The wound is ooze yeloow pus. The wound obtained a week ago due to fall while playing soccer. Four days ago he went to the doctor and been given some medicine but is not getting better. After physical examination, the doctor ask for laboratory examination as Gram staining for the pus. After few minttes, the Gram staining result sight at the microscope is visible colonies of blue bacteria, spherical shape and clusters like grapes fruit. 1. What bacteria that visible at the microscope for this case? 2. Explain the differences in the characteristics of gram-negative and gram-positive bacteria ! 3. Explain why each bacteria produce different colors in Gram staining ! 4. Identify each five (5) examples of Gram Positive and Gram Negative Bacteria ! 5. Describe the structure of Gram-negative bacteria cell wall ! 6. . Describe the structure of Gram-positif bacteria cell wall ! 7. Explain the benefits of knowing the classification of bacteria based on the results of gram staining ! Self Assessment: 1. Explain the steps of Gram staining ! Reff : Jawetz, Melnick, Adelberg. 2013 Chapter 3. Classification of Bacteria in Medical Microbiology, 26th Edition by Vishal . The McGraw-Hill Companies. Lange Microbiology. LECTURE 22 MYCOBACTERIUM IB Nyoman Putra Dwija, S.Si, M. Biotech ABSTRACT Genus of Mycobacterium consist of many species that potentially pathogen such as Mycobacterium complex (M.tuberculosis, M.bovis, M.africanum), M.leprae and M.ulcerans. All the member of the genus has the similar properties Which is thin, slightly curved or straight rod-shaped (0.2-0.4 X 2 – 10 µm), non motile, grow slowly, aerobe, non sporoforming, non motile and pigment of the colony are varies from non pigmented to pigmented. Tuberculosis (Tb) is an ancient diseases that found more than 100 year ago, which is still have a high number of cases. In a predicted as much as 9 million people are infected and more than 2 million death annualy. Mycobacterium tuberculosis (M.Tb) is the only agent of Tb, M.Tb was identified for the first time by Robert Koch in 1882, while he Udayana University Faculty of Medicine, DME, 2016 34 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases was presenting his famous postulate. Mycobacteria spp have a different structure of cell wall which contain N- glycolylmuramic and rich content of lipid. Because of this unusual cell wall, mycobacteria are dificult to stain with basic anyline dye such as Gram staining, but once the bacteria stained, it’s dificult to decolorization even with acidified alcohol (3% HCL), and so called Acid fast bacilli. HIV Pandemic and emerging of MDR/XDR-TB is another problem that treathed a human health. Another member of genus of Mycobacterium is Mycobacterium leprae,the etiologic agent of Leprosy (Hansen diseases). Majority of the cases found in South and Southeast Asia, Africa and Latin America,with number of cases average 600.000-700.000 annualy. Leprosy is a chronic, granulomatous and delibitating diseases. General manifestation is anasthetic skin lesion and peripheral neuropathy with tickening of the nerve. Bacilli can be found from few (Tuberculoid leprosy) to massive number of bacteria (Lepromatous leprosy). Since the bacteria is dificult tu culture, diagnosis is based on finding of the diseases sign with suported by AFB finding in the slit skin smear or biopsy, molecular detection as well. LEARNING TASK A 45 years old women come to the private clinic with productive cought,with blood on the sputum since 2 weeks, sweating in the night, loses in body weight and loses of apetite 1. What is the posible diagnosis of this patient? 2. Explain the properties of the etiologic agent of deseases! 3. What is the best specimen must be collected for laboratory examination? 4. As a doctor what is your suggestion for this patient? 5. What is latent tuberculosis? SELF ASSESSMENT: 1. What is the relationship between HIV and TB 2. What is MDR and XDR TB and How did it happen? 3. What is the role of the lipid rich of the wall on the staining? 4. What staining can be use to detect M. tuberculosis? 5. Explain about: Tubercolous tuberculosis, Non tuberculous tuberculosis, Tb Extrapulmonal? LECTURE 23 PATHOGENESIS OF VIRAL INFECTION Dr. dr. Ni Nyoman Sri Budayanti, SpMK Abstract Viral pathogenesis is the process by which viruses produce disease in the host. The factors that determine the viral transmission, multiplication, and development of disease in the host involve complex and dynamic interactions between the virus and the susceptible host. Viruses cause disease when they breach the host's primary physical and natural protective barriers; evade local, tissue, and immune defenses; spread in the body; and destroy cells either directly or via bystander immune and inflammatory responses. Pathogenic Udayana University Faculty of Medicine, DME, 2016 35 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases mechanisms of viral disease include ; implantation of virus at the portal of entry, local replication, spread to target organs (disease sites), and spread to sites of shedding of virus into the environment. Factors that affect pathogenic mechanisms are accessibility of virus to tissue, cell susceptibility to virus multiplication, and virus susceptibility to host defenses. Learning Task A 5-year old boy goes to emergency room because of fever, rash, cold and cough. On physical examination was found Koplik spots on his bucosal mukosa Question: 1. What is the meaning of Koplik spots 2. What kind of viruses can make Koplik spots 3. Describe how the virus can enter to the human body 4. Describe the complication of this disease Self Assesment 1. Describe the clasification of viruses 2. Describe the simptoms and signs of viral infection 3. Describe how the viruses can enter to the human body 4. Describe the effect of viral infection in the cellular level 5. Describe the replication of viruses in general 6. Describe how the viruses can spread from human to human LECTURE 24 DNA VIRUS Dr. dr. Ni Nyoman Sri Budayanti, SpMK Abstract Viruses can be classified based on proteins encoded within the viral genetic material or genomic. DNA virus is a virus that has DNA as its genetic mterial and replicates using DNAdependent DNA polymerase. In the appropriate cell, DNA viruses are able to program the cell to replicate the virus using the genes contained within the viral DNA genome. There are six different DNA virus families that infect and may cause significant disease in humans. Viruses with small DNA genomes include human papillomavirus (HPV). HPV infects epithelial cells of the skin. It causes common warts on hands and feet and in some cases is important for the development of cervical cancer in woman. Hepatitis B is another small DNA virus that infects the liver, causes hepatitis, and is associated with liver cancer. Adenovirus, herpesvirus, and poxvirus are all examples of large DNA viruses that infect humans. Adenovirus cause gastroenteritis and respiratory disease in humans. Learning task Describe in detail the clasification of DNA viruses base on Baltimore’s clasification and example of the viruses from each classes Explain in detail 3 viruses (Hepatitis virus, Herpes virus, Human papiloma virus) which are belong to DNA viruses based on their : o Baltimore’s clasification o Structure of their virion Udayana University Faculty of Medicine, DME, 2016 36 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases o o o o Replication Route of shedding and spreading Simptoms and signs Complication Self Assesment A 30-year old woman goes to private clinic because of fever, fatique, malaise, jaundice and dark urine. Her boy friend has addmited in hospital last month due to similar simptoms. Question: 1. What kind virus as the causes of that illness. 2. Which Baltimore’s clasification is the virus belong to 3. How can the virus enter our body 4. How can the virus infect her 5. What kind treatment can be given to her LECTURE 25 RNA VIRUS Dr. dr. Ni Nyoman Sri Budayanti, SpMK Abstract An RNA virus is a virus that has RNA (ribonucleic acid) as the genetic material. Notable human diseases caused by RNA viruses include Ebola, Hemorrhagic fever, SARS, Influenza, Hepatitis C, Polio and measles. RNA generally have very high mutation rate compare to DNA viruses, because virus RNA polymerase lact the proof-reading ability of DNA polymerase. Classification is based on the type of genomes and gene number and organitation. Learning task 1. Describe the structure of RNA viruses 2. Describe classification RNA viruses based on their type of genome 3. Describe replication of RNA virus, particullary retroviruses 4. Explain 3 kinds of RNA viruses (rabies, influenza, polio) based on their : Structure of virion Replication Mode of transmition Pathogenesis Simptom and signs Treatment Self assesment A 5-year old boy come to emergency room because of panic, dificult to swallow, avoid light and hidrofobi. His parent told that he has been bitten by dog 2 month ago and no vaccination was given. Question What kind simptom and sign were specific for this illness Udayana University Faculty of Medicine, DME, 2016 37 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases What kind virus is cause of this illnes Explain in detail the vaccination should be receive to prevent this illness LECTURE 26 ZOONOSIS Dr. dr. Ni Nyoman Sri Budayanti, SpMK Abstract Any disease of infection that is naturally transmissible from vertebrate animals to humans and vice versa is classified as a zoonosis. Zoonoses have been recognized for many centuries. They are caused by all types of pathogenic agent including bacteria, parasites, fungi and viruses. Zoonosis still represent significant publict health threats but many of them a negleted i.e. they are not priotized by health system at national and international level. They affect people especially in developing country although most of them can be prevent. Learning task 1. Namely 5 diseases which are including in zoonosis diseases and explain why those of them fit with zoonosis criteria. 2. Explain in detail why One Health approach is a good stategic to prevent and overcome problem of zoonosis disease Self assesment A 23-year old man come to emergency room because of fever, hard to breathe since 2 days ago. In 2 days he felt the simptom getting worse. He has history contacted with dead chicken in his farm. Question What kind disease has he suffering What kind microorganism as cause of that illness How to prevent that illness LECTURE 27 SPECIMEN COLLECTION dr. Ni Nengah Dwi Fatmawati, SpMK, Ph.D Abstract Infectious diseases are caused by microbes, including bacteria and viruses. Identification of microbes as causative agents of infection is important to help in determining definitive therapy. Clinical specimens from patients such as blood, sputum, urine, wound swab, etc., are needed for Clinical Microbiology assay for microbes identification and antimicrobial susceptibility test. Correct and proper specimen must be collected for the assay. There are considerations that must be concerned when collecting specimen for Clinical Microbiology for example proper time collection, proper site of collection, volume or number of specimen, Udayana University Faculty of Medicine, DME, 2016 38 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases avoid contamination, etc., therefore the results of assay will be reliable and can assist the clinicians to treat the infectious diseases properly. Learning Task: Case 1: A 30-year-old woman goes to private clinic because of dysuria, frequency, and urgency on urination for 24 hours. Questions: 1. What kind of specimen(s) must be collected from this patient? 2. How to collect the specimen(s) therefore get proper specimen? 3. How to transport and preserve the specimen(s)? Case 2: A-70-year old man admitted to ER with chief complain harsh, productive cough since 4 days prior to being seen by a physician. The sputum is thick and yellow with blood streaks. He had fever, shaking, chills and malaise along with the cough. Questions: 1. What kind of specimen(s) must be collected from this patient? 2. How to collect the specimen(s) therefore get proper specimen? 3. How to transport and preserve the specimen(s)? Self assesment: 1. Describe general considerations of clinical specimen collection for clinical microbiology assay. 2. Describe in detail how to collect, transport and preserve blood specimen. 3. Describe in detail how to collect, transport and preserve sputum specimen. 4. Describe in detail how to collect, transport and preserve urine specimen. 5. Describe in detail how to collect, transport and preserve wound aspiration specimen. 6. Describe in detail how to collect, transport and preserve wound swab specimen. 7. Describe in detail how to collect, transport and preserve throat swab specimen. 8. Describe in detail how to collect, transport and preserve cerebrospinal fluid (CSF) specimen. 9. Determine proper specimen for diagnose: a. Urinary tract infections b. Pneumonia c. Sepsis d. Infected wound e. Meningitis f. Pharingitis 10. How to avoid normal flora contamination when collecting urine and sputum specimen? References: Mahon et al., Textbook of Diagnostic Microbiology, Fourth Edition, Elsevier, 2011 Udayana University Faculty of Medicine, DME, 2016 39 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases LECTURE 28 MICROBIAL IDENTIFICATION & ANTIMICROBIAL SENSITIVITY TEST (AST) dr. Ni Nengah Dwi Fatmawati, SpMK, Ph.D Abstract Proper clinical specimen is needed for reliable result of Clinical Microbiology Tests. After collecting the specimen, specimen is subjected to several Clinical Microbiology examinations or tests to identify the causative agents of infections. The specimen generally will be subjected to staining (for example Gram staining, Ziehl Neelsen staining), culture, biochemical tests for identification, or molecular biology tests for further identification. The microbial (bacterial) identification is followed by antisusceptibility testing (AST) to determine the susceptibility of tested bacteria to certain antibiotics. The bacterial identification and AST can be done manually, semi automatically or automatically. The result of bacterial identification and AST will help the clinicians to determine definitive therapy of antibiotics. Learning task: Case: A-50-year old man admitted to ER with chief complain productive cough since 7 days prior to being seen by a physician. The sputum is thick and yellow with blood streaks. He had fever, shaking, chills and malaise along with the cough. Sputum specimen was taken. Question: 1. Explain steps for bacterial identification for this patient. 2. Explain steps for the AST for this patient (using Kirby Bauer Disk Difussion). Antibiotics that used for this case is Ciprofloxacin, Ampicillin, Amoxyxillin, Cefadroxil, and Gentamicin. 3. Explain the result iof AST if the result showed like this. Table from CLSI (only simulation) Antibiotics’ name Ciprofloxacin Ampicillin Amoxycillin Cefadroxil Gentamicin Range for Susceptible/S (mm) > 25 > 20 > 17 > 22 > 18 Range for Intermediate/I (mm) 15-25 11-20 10-17 15-22 11-18 Range for Resistant/R (mm) < 15 < 11 < 10 < 15 < 11 Result of This Case’s AST (mm) 30 8 15 23 19 Self assesment: 1. Describe how to identify Staphylococcus (based on Gram staining, colony on culture, and biochemical tests). 2. Describe how to identify Streptococcus (based on Gram staining, colony on culture, and biochemical tests). 3. Explain or give examples of manual, semi-automatic, and automatic bacterial identification. Udayana University Faculty of Medicine, DME, 2016 40 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases 4. Explain how to identify Mycobacterium tuberculosis (based on Ziehl Neelsen staining and colony characteristic on culture) 5. Explain how to perform Kirby Bauer Disk Diffusion Tests and how to interpret the result. References: Mahon et al., Textbook of Diagnostic Microbiology, Fourth Edition, Elsevier, 2011 LECTURE 29 MECHANISM OF ACTION AND RESISTANCE OF ANTIBIOTIC dr. Ni Nengah Dwi Fatmawati, SpMK, Ph.D Abstract Antibiotics are therapy for bacterial infections. Antibiotics can be used as empirical, definitive, and prophyoaxis therapy. There are several mechanism of action of antibiotics i.e., Inhibition of Cell Wall Synthesis (Beta lactam, Vancomycin, Bacitracin), Inhibition of Protein Synthesis (Aminoglycosides, Tetracyclin, Chloramphenicol, Macrolides, Clindamycin), Alteration of Cell Membrane (Polymixins), Inhibition of Nucleic Acid Synthesis (Quinolone, Metronidazole, Rifampin), and Antimetabolite Activity (TMP-SXT). Considerations are needed for prudent use of antibiotics. Misuse of antibiotics will encourage the resistance against the antibiotics. Several mechanism involve in bacterial resistance. Learning Task: Case: A 20-year-old woman goes to GP because of dysuria, frequency, and urgency on urination for 24 hours. The bacterial identification of bacteria showed Escherichia coli (105 colony count) and susceptible to Trimethoprim-Sulphametoxazole (TMP-SXT) and Ciprofloxacin. Questions: 1. Explain the mechanism of action TMP-SXT and the resistance mechanism against TMP-SXT. 2. Explain the mechanism of action Ciprofloxacin and the resistance mechanism of Ciprofloxacin 3. Explain how the antimicrobial resistant genes are transferred via conjugation, transduction, transformation and transposition 4. Explain other antibiotics that are classified as quinolone. Self Asessment: 1. Explain classes of antibiotics and give examples of each clasess 2. Explain the mechanism of action of each antibiotic class 3. Explain the mechanism of resistance to each classes of antibiotics 4. Explain what are the empirical, definitive and prophylaxis antibiotics 5. Explain the consideration for prudent use of antibiotics References: Udayana University Faculty of Medicine, DME, 2016 41 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases Jawetz, Melnick & Adelberg’s Medical Microbiology. 26th Ed, 2013. LECTURE 30 BIOSAFETY & BIOSECURITY IB Nyoman Putra Dwija, S.Si, M. Biotech ABSTRACT Biosafety and biosecurity issues began to develop since the occurrence of some of the pandemic in some countries of the world, such as bird flu, swine flu and the case envelopes containing anthrax. Biosafety and biosecurity not just concenrn obout the biologic agent but also concerned about the issue of bioterrorism, good laboratory practice, risk group of the potentially pathogen and also the safety of the environment. Material transfer agreement also become one of the study in the biosafety and biosecurity so that, the biological material is not misused and there is an agreement between two parties in its management. LEARNING TASK A 23 years old man work as a cleaning service in the research laboratorium, he come to the clinic because of feel afraid after sticking by needle in the bin while he work. 1. What is the posibility of misconduct in this cases? 2. Why we should keep our specimen in the special container? 3. What is the role of biosafety and biosecurity oon that case? 4. What is the role of standart operational procedure in the laboratory? SELF ASSESSMENT 1. Explain about risk group of organism 2. What we need when we are working with M.tuberculosis? 3. What is containment? Please explain! 4. What is good laboratory practice? LECTURE 31 HEALTH CARE-ASSOCIATED INFECTION Dr. dr. I Dewa Made Sukrama, M. Si, Sp.MK ABSTRACT Health care-associated infection (HAI) — also known as nosocomial infection — is an infection that is contracted from the environment or staff of a healthcare facility. It can be spread in the hospital environment, nursing home environment, rehabilitation facility, clinic, or other clinical settings. Infection is spread to the susceptible patient in the clinical setting by a number of means. Health care staff can spread infection, in addition to contaminated equipment, bed linens, or air droplets. The infection can originate from the outside environment, another infected patient, staff that may be infected, or in some cases, the source of the infection cannot be determined. In some cases the microorganism originates from the patient's own skin microbiota, becoming opportunistic after surgery or other procedures that compromise the protective skin barrier. Though the patient may have Udayana University Faculty of Medicine, DME, 2016 42 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases contracted the infection from their own skin, the infection is still considered nosocomial since it develops in the health care setting In the United States, the Centers for Disease Control and Prevention estimated roughly 1.7 million hospital-associated infections, from all types of microorganisms, including bacteria and fungi combined, cause or contribute to 99,000 deaths each year.[citation needed] In Europe, where hospital surveys have been conducted, the category of gram-negative infections are estimated to account for two-thirds of the 25,000 deaths each year. Nosocomial infections can cause severe pneumonia and infections of the urinary tract, bloodstream and other parts of the body. Many types are difficult to treat with antibiotics. In addition, antibiotic resistance can complicate treatment. Learning Task 1. Describe risk factors are influence hospital acquired infection 2. Describe some strategies for control of hospital acquired infection 3. Describe some factors are influence to spread of hospital acquired infection. 4. Explain the prevention hospital acquired infection 5. Explain the sources and routes of spread of Hospital Acquired Infection LECTURE 32 ANAEROB BACTERIA & SPIROCHAETA Dr. dr. I Dewa Made Sukrama, M. Si, Sp.MK ABSTRACT Anaerobic infections are caused by anaerobic bacteria. Obligately anaerobic bacteria do not grow on solid media in room air (0.04% carbon dioxide and 21% oxygen); facultatively anaerobic bacteria can grow in the presence or absence of air. Microaerophilic bacteria do not grow at all aerobically or grow poorly, but grow better under 10% carbon dioxide or anaerobically. Anaerobic bacteria can be divided into strict anaerobes that can not grow in the presence of more than 0.5% oxygen and moderate anaerobic bacteria that are able of growing between 2 and 8% oxygen. Anaerobic bacteria usually do not possess catalase, but some can generate superoxide dismutase which protects them from oxygen. .The frequency of isolation of anaerobic bacterial strains varies in different infectious sites.Mixed infections caused by numerous aerobic and anaerobic bacteria are often observed in clinical situations. Anaerobic bacteria are a common cause of infections, some of which can be serious and life-threatening. Because anaerobes are the predominant components of the normal flora of the skin and mucous membranes, they are a common cause infections of endogenous origin. Because of their fastidious nature, anaerobes are hard to culture and isolate and are often not recovered from infected sites. The administration of delayed or inappropriate therapy against these organisms may lead to failures in eradication of these infections. The isolation of anaerobic bacteria requires adequate methods for collection, transportation and cultivation of clinical specimens.The management of anaerobic infection is often difficult because of the slow growth of anaerobic organisms, which can delay their identification by the frequent polymicrobial nature of these infections and by the increasing resistance of anaerobic bacteria to antimicrobials. Udayana University Faculty of Medicine, DME, 2016 43 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases LEARNING TASK 1. Discrebe the anaerobic gram positive bacteria 2. Discrebe the gram negative anaerob bacteria 3. Be able to describe the genus clostridia and specific deseases 4. Explain how diagnosis microbiology anaerobic infection LECTURE 33 HOST RESPONSE TO INFECTION Prof. Dr. dr. Tuti Parwati Merati, SpPD, KPTI Abstract Infectious diseases are one of the leading causes of death worldwide. Many infectious diseases become difficult to control if the infectious agents evolve resistance to commonly used drugs, for example, bacteria can accumulate mutations in their DNA or acquire new genes that allow them to survive contact with antibiotic drugs that would normally kill them. Scientists are currently searching for new approaches to treat infectious diseases, focusing on exactly how the pathogens change and drug resistance evolves. Understanding and comprehend the host response to infection is important. Infection process After invading the body, microorganisms must multiply to cause infection. After multiplication begins, one of three things can happen: 1. Microorganisms continue to multiply and overwhelm the body’s defenses. 2. A state of balance is achieved, causing chronic infection. 3. The body—with or without medical treatment—destroys and eliminates the invading microorganism. Defenses Against Infection Host defenses that protect against infection : – Natural barriers (eg, skin, mucous membranes) – Nonspecific immune responses (eg, phagocytic cells [neutrophils, macrophages] and their products) – Specific immune responses (eg, antibodies, lymphocytes) Nonspecific Immune Responses • Cytokines (including IL-1, IL-6, tumor necrosis factor-alpha, and interferon-gamma) are produced principally by macrophages and activated lymphocytes and mediate an acute-phase response that develops regardless of the inciting microorganism. • The response involves fever and increased production of neutrophils by the bone marrow. Endothelial cells also produce large amounts of IL-8, which attracts neutrophils. • The inflammatory response directs immune system components to injury or infection sites and is manifested by increased blood supply and vascular permeability, which allows chemotactic peptides, neutrophils, and mononuclear cells to leave the intravascular compartment. Specific Immune Responses • After infection, the host can produce a variety of antibodies (complex glycoproteins known as immunoglobulins) that bind to specific microbial antigenic targets. Udayana University Faculty of Medicine, DME, 2016 44 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases Antibodies can help eradicate the infecting organism by attracting the host’s WBCs and activating the complement system. • The complement system destroys cell walls of infecting organisms, usually through the classical pathway. Complement can also be activated on the surface of some microorganisms via the alternative pathway. • Antibodies can also promote the deposition of substances known as opsonins (eg, the complement protein C3b) on the surface of microorganisms, which helps promote phagocytosis. Opsonization is important for eradication of encapsulated organisms such as pneumococci and meningococci. Interaction between host and the microbes are depend on factors from the host, the microbes and environment Host Genetic Factors • For many pathogens, the host's genetic make-up influences the host's susceptibility and the resulting morbidity and mortality. For example, patients who have deficiencies of the terminal complement components (C5 through C8, perhaps C9) have an increased susceptibility to infections caused by neisserial species. Factors Facilitating Microbial Invasion Microbial invasion can be facilitated by the following: • Virulence factors • Microbial adherence, biofilm • Resistance to antimicrobials • Defects in host defense mechanisms Defects in Host Defense Mechanisms Two types of immune deficiency states affect the host’s ability to fight infection: • Primary immune deficiency : are genetic in origin; > 100 primary immune deficiency states have been described. Most primary immune deficiencies are recognized during infancy; however, up to 40% are recognized during adolescence or adulthood. • Secondary (acquired) immune deficiency : are caused by another disease (eg, cancer, HIV infection, chronic disease) or by exposure to a chemical or drug that is toxic to the immune system. Defects in immune responses may involve • Cellular immunity • Humoral immunity • Phagocytic system • Complement system Mechanism • Cellular deficiencies are typically T-cell or combined immune defects. T cells contribute to the killing of intracellular organisms; thus, patients with T-cell defects can present with opportunistic infections such as Pneumocystis jirovecii or cryptococcal infections. Chronicity of these infections can lead to failure to thrive, chronic diarrhea, and persistent oral candidiasis. • Humoral deficiencies are typically caused by the failure of B cells to make functioning immunoglobulins. Patients with this type of defect usually have infections involving encapsulated organisms (eg, H. influenzae, streptococci). Patients can present with poor growth, diarrhea, and recurrent sinopulmonary infections. Udayana University Faculty of Medicine, DME, 2016 45 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases • A defect in the phagocytic system affects the immediate immune response to bacterial infection and can result in development of recurrent abscesses or severe pneumonias. • Primary complement system defects are particularly rare. Patients with this type of defect may present with recurrent infections with pyogenic bacteria (eg, encapsulated bacteria, Neisseria sp) and have an increased risk of autoimmune disorders (eg, SLE). Clinical manifestation • Most infections increase the pulse rate and body temperature, but others (eg, typhoid fever, tularemia, brucellosis, dengue) may not elevate the pulse rate commensurate with the degree of fever. • Hypotension can result from hypovolemia, septic shock, or toxic shock. Hyperventilation and respiratory alkalosis are common. • Alterations in sensorium (encephalopathy) may occur in severe infection regardless of whether CNS infection is present. Encephalopathy is most common and serious in the elderly and may cause anxiety, confusion, delirium, stupor, seizures, and coma. • Infectious diseases commonly increase the numbers of mature and immature circulating neutrophils. Mechanisms include demargination and release of immature granulocytes from bone marrow, IL-1- and IL-6-mediated release of neutrophils from bone marrow, and colony-stimulating factors elaborated by macrophages, lymphocytes, and other tissues. Exaggeration of these phenomena (eg, in trauma, inflammation, and similar stresses) can result in release of excessive numbers of immature leukocytes into the circulation (leukemoid reaction), with leukocyte counts up to 25 to 30 × 109/L. • Conversely, some infections (eg, typhoid fever, brucellosis) commonly cause leukopenia. In overwhelming, severe infections, profound leukopenia is often a poor prognostic sign. • Characteristic morphologic changes in the neutrophils of septic patients include Döhle bodies, toxic granulations, and vacuolization. • Anemia can develop despite adequate tissue iron stores. If anemia is chronic, plasma iron and total iron-binding capacity may be decreased. Serious infection may cause thrombocytopenia and disseminated intravascular coagulation (DIC). Learning Tasks: A 40 years-old female admitted to hospital with decreased of consciousness. She suffering from high fever since a week ago, and she also did not eat and drink much as for her weaknesses. She had headache, sometimes vomits and feel abdominal discomfort. 1. What is the working diagnosis of the patient? 2. What kind of examination do you need to do for this patient? 3. Please explain if there is a possibility of a defective imune response in this patient? Self Assessment: 1. Describe the host response to infection in this patient. 2. Based on the pathogenesis, please describe the management of the patient. Udayana University Faculty of Medicine, DME, 2016 46 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases LECTURE 34, 35, 36 DENGUE FEVER, DENGUE HEMORRHAGIC FEVER, DENGUE SHOCK SYNDROME dr. Dewi Dian Sukmawati, SpPD ABSTRACT Dengue is mosquito borne viral infection, which causing acute fever and occasionally develops into potential lethal complication. Dengue virus is transmitted by female mosquitoes mainly of the species Aedes aegypti and, to a lesser extent, Ae. albopictus. This mosquito also transmits Chikungunya, Yellow Fever and Zika infection. About half of world’ population were at risk, Dengue is widespread throughout the tropics, with local variations in risk influenced by rainfall, temperature and unplanned rapid urbanization. There are 4 distinct, but closely related, serotypes of the virus that can cause dengue (DEN-1, DEN-2, DEN-3 and DEN-4). Recovery from infection by one provides lifelong immunity against the particular serotype with partial and temporary cross-immunity to the other serotypes after recovery. Subsequent infections by other serotypes increase the risk of developing severe dengue. Dengue should be suspected when a high fever is present, accompanied by 2 of the following symptoms: severe headache, pain behind the eyes, muscle and joint pains, nausea, vomiting, swollen glands or rash. Symptoms usually last for 2–7 days, after an incubation period of 4 – 5 days (range 3 – 14 days) after the bite from an infected mosquito. Severe dengue is a potentially deadly complication due to plasma leakage, fluid accumulation, respiratory distress, severe bleeding, or organ impairment. Warning signs occur 3–7 days after the first symptoms in conjunction with a decrease in temperature and include: severe abdominal pain, persistent vomiting, and rapid breathing, bleeding gums, fatigue, restlessness and blood in vomit. The next 24–48 hours of the critical stage can be lethal; proper medical care is needed to avoid complications and risk of death. For the purpose of clinical management, WHO classifies dengue illness as (i) dengue with or without warning signs for progression towards severe dengue and (ii) severe dengue. Warning signs of severe dengue include abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy or restlessness, liver enlargement of >2 cm, or an increase in Hematocrit concurrent with a rapid decrease in platelet count. Criteria for severe dengue include any sign of severe plasma leakage leading to shock or fluid accumulation with respiratory distress, severe bleeding, or severe organ impairment. There is no specific treatment for dengue, maintenance of the patient’s body fluid volume is critical in management of severe dengue. Vaccine for prevention is now commercially available, Dengvaxia (CYD – TDV) for use in individual age 9 – 45 years living in area with high burden of disease. LEARNING TASK Case 1: IMD, 16 year old male student come to a private clinic with acute onset of high fever. The fever starts abruptly one day before accompanied by nausea and retro orbital pain. Udayana University Faculty of Medicine, DME, 2016 47 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases Questions: 1. What other information needed in anamnesis of this patient? What data should be obtained during physical examination? 2. The evaluation shows vital sign was stabile without any sign of bleeding, the patient able to drink plenty and eat normally. What is the diagnosis of this patient? How about further plan for this case, including planning for diagnostic, treatment, monitoring and patient and family’s education? 3. The next day, he showed his laboratory evaluation. WBC: 1.03 x 103/uL. Hb. 17 g/dL. HCT 54 %. Plt. 98 x 103/uL. What is the diagnosis of this patient? How about further plan for this case, including planning for diagnostic, treatment, monitoring and patient and family’s education? Case 2: 25 year old woman, working as a private secretary, come to the clinic with 4 days of fever. Since morning she also had her menstrual bleeding which comes 2 weeks early. The initial evaluation revealed moderately ill, fully alert. Blood pressure 90/76 mmHg. Pulse rate 124 x/minutes. Respiratory rate: 22 x/minutes. Temperature axillae: 36.7˚C. Hepatomegaly 3 cm below costal arch, tender on palpation, the acrals were cold. She has her laboratory evaluation: WBC: 3.02 x 103/uL; Hb. 16 g/dL. HCT: 51.2 %. Plt.32 x 103/uL 1. What is the diagnosis of this patient? How about further plan for this case, including planning for diagnostic, treatment, monitoring and patient and family’s education? 2. Is there any indication for platelet transfusion in this case? Why? 3. The patient was then hospitalized, by the third day of her hospital stay, she complain about shortness of breath and cough if she change position from supine to sitting. The physical evaluation revealed dullness on lower part of right hemithorax with decreased breath sounds. What kind of complication can be expected in severe dengue cases? How can we establish the diagnosis? Self assessment 1. How can we differentiate between dengue fever and dengue hemorrhagic fever? Make a comparison chart on this issue! 2. Both DHF grade 3 and 4 are included as DSS. How can we differentiate between the two of them? 3. What is NS1 dengue antigen? When is the best way to use it? 4. How about dengue serology? When IgM anti-Dengue become positive? When the Ig G anti-dengue become positive? Make the chart on the possible result and its interpretation! REFERENCES: 1. World Health Organization. Dengue Guidelines for Diagnosis, Treatment, Prevention and Control. Geneva, Switzerland: 2009. Available at http://www.who.int/tdr/ publications/documents/dengue-diagnosis.pdf 2. Messina JP, et al. Global spread of dengue virus types: mapping the 70 year history. Trends Microbiol. 2014;22(3):138–146. 3. Guzman MG, et al. Dengue. Lancet. 2015;385(9966):453–465. 4. Comprehensive guidelines for prevention and control of dengue and dengue hemorrhagic fever. WHO SEARO 2011 5. Handbook for clinical management of dengue. WHO 2012 Udayana University Faculty of Medicine, DME, 2016 48 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases LECTURE 37 INFECTION IN PREGNANCY (TORCH) Dr. dr. IB Fajar Manuaba, SpOG Abstract Infections have historically been a major cause of maternal and fetal morbidity and mortality worldwide, and they remain so in the 21st century. The unique maternal-fetal vascular connection in some cases serves to protect the fetus from infectious agents, whereas in other instances it provides a conduit for their transmission to the fetus. TORCH infections include infections associated with Toxoplasma, Other organisms (Parvovirus, human immunodeficiency virus, Epstein-Barr virus, herpesviruses 6 and 8, varicella, syphilis, enteroviruses), Rubella, Cytomegalovirus (CMV), and Hepatitis. Despite the recent emphasis in the screening, antibiotic prophylaxis, and management of early-onset many neonates and children yearly experience the consequences of classic perinatal infections Introduction Infections have historically been a major cause of maternal and fetal morbidity and mortality worldwide, and they remain so in the 21st century. The unique maternal-fetal vascular connection in some cases serves to protect the fetus from infectious agents, whereas in other instances it provides a conduit for their transmission to the fetus. Maternal serological status, gestational age at the time infection is acquired, the mode of acquisition, and the immunological status of both the mother and her fetus all influence disease outcome. TORCH is an acronym for a group of congenitally acquired infections that may cause significant morbidity and mortality in neonates. TORCH infections include infections associated with Toxoplasma, Other organisms (Parvovirus, human immunodeficiency virus, Epstein-Barr virus, herpesviruses 6 and 8, varicella, syphilis, enteroviruses), Rubella, Cytomegalovirus (CMV), and Hepatitis. Despite the recent emphasis in the screening, antibiotic prophylaxis, and management of early-onset many neonates and children yearly experience the consequences of classic perinatal infections. Toxoplasmosis The obligate intracellular parasite Toxoplasma gondii has a life cycle with two distinct stages. The feline stage takes place in the cat—the definitive host—and its prey. Unsporulated oocysts are secreted in feces. In the non-feline stage, tissue cysts containing bradyzoites or oocysts are ingested by the intermediate host, including humans. Human infection is acquired by eating raw or undercooked meat infected with tissue cysts or by contact with oocysts from cat feces in contaminated litter, soil, or water. Prior infection is confirmed by serological testing, and its prevalence depends on geographic locale and parasite genotype. Most acute maternal infections are subclinical and are detected only by prenatal or newborn serological screening. In some cases, maternal symptoms may include fatigue, fever, headache, muscle pain, and sometimes a maculopapular rash and posterior cervical lymphadenopathy. The incidence and severity of fetal toxoplasmosis infection depend on gestational age at the time of maternal infection. Risks for fetal infection increase with Udayana University Faculty of Medicine, DME, 2016 49 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases pregnancy duration A metaanalysis estimated the risk to be 15 percent at 13 weeks, 44 percent at 26 weeks, and 71 percent at 36 weeks. Conversely, the severity of fetal infection is much greater in early pregnancy, and these fetuses are much more likely to have clinical findings of infection. Pregnant women suspected of having toxoplasmosis should be tested. The parasite is rarely detected in tissue or body fluids. Anti-toxoplasma IgG develops within 2 to 3 weeks after infection, peaks at 1 to 2 months, and usually persists for life—sometimes in high titers. Although IgM antibodies appear by 10 days after infection and usually become negative within 3 to 4 months, they may remain detectable for years. Thus, IgM antibodies should not be used alone to diagnose acute toxoplasmosis. IgA and IgE antibodies are also useful in diagnosing acute infection. Toxoplasma IgG avidity increases with time. Thus, if a high-avidity IgG result is found, infection in the preceding 3 to 5 months is excluded. Multiple commercial avidity tests are now available that provide a 100-percent positive predictive value of high avidity confirming latent infection. No randomized clinical trials have been performed to assess the benefit and efficacy of treatment to decrease the risk for congenital infection. A systematic review of data from 1.438 treated pregnancies found weak evidence for early treatment to reduce congenital toxoplasmosis risks. Treatment has been associated with a reduction in rates of serious neurological sequelae and neonatal demise. Prenatal treatment is based on two regimens—spiramycin alone or a pyrimethamine– sulfonamide combination with folinic acid. These two regimens have also been used consecutively. Little evidence supports the use of a specific regimen. That said, most experts will use spiramycin in women with acute infection early in pregnancy. Pyrimethamine–sulfadiazine with folinic acid is selected for maternal infection after 18 weeks or if fetal infection is suspected. Parvovirus Human parvovirus B19 causes erythema infectiosum, or fifth disease. The B19 virus is a small, single-stranded DNA virus that replicates in rapidly proliferating cells such as erythroblast precursors. This can lead to anemia, which is its primary fetal effect. Only individuals with the erythrocyte globoside membrane P antigen are susceptible. In women with severe hemolytic anemia—for example, sickle-cell disease—parvovirus infection may cause an aplastic crisis. In 20 to 30 percent of adults, infection is asymptomatic. Fever, headache, and flu-like symptoms may begin in the last few days of the viremic phase. Several days later, a bright red rash with erythroderma affects the face and gives a slappedcheekappearance. The rash becomes lacelike and spreads to the trunk and extremities. Adults often have milder rashes and develop symmetrical polyarthralgia that may persist several weeks. There is vertical transmission to the fetus in up to a third of maternal parvovirus infections Fetal infection has been associated with abortion, nonimmune hydrops, and stillbirth. In a review of 1089 cases of maternal B19 infection from nine studies, Crane (2002) reported an overall fetal loss rate of 10 percent. It was 15 percent for infections before 20 weeks but was only 2.3 percent after 20 weeks. Udayana University Faculty of Medicine, DME, 2016 50 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases Depending on gestational age, fetal transfusion for hydrops may improve outcome in some cases. Mortality rates as high as 30 percent have been reported in hydropic fetuses without transfusions. With transfusion, 94 percent of hydrops cases resolve within 6 to 12 weeks, and the overall mortality rate is < 10 percent. Most fetuses require only one transfusion because hemopoiesis resumes as infection resolves. There is currently no approved vaccine for human parvovirus B19, and there is no evidence that antiviral treatment prevents maternal or fetal infection. Decisions to avoid higher-risk work settings are complex and require assessment of exposure risks. Pregnant women should be counseled that risks for infection approximate 5 percent for casual, infrequent contact; 20 percent for intense, prolonged work exposure such as for teachers; and 50 percent for close, frequent interaction such as in the home. Workers at day-care centers and schools need not avoid infected children because infectivity is greatest before clinical illness. Finally, infected children do not require isolation. Rubella—German Measles This RNA togavirus typically causes infections of minor importance in the absence of pregnancy. Rubella infection in the first trimester, however, poses significant risk for abortion and severe congenital malformations. Transmission occurs via nasopharyngeal secretions, and the transmission rate is 80 percent to susceptible individuals. The peak incidence is late winter and spring. Maternal rubella infection is usually a mild, febrile illness with a generalized maculopapular rash beginning on the face and spreading to the trunk and extremities. Other symptoms may include arthralgias or arthritis, head and neck lymphadenopathy,and conjunctivitis. The incubation period is 12 to 23 days. Viremia usually precedes clinical signs by about a week, and adults are infectious during viremia and through 5 to 7 days of the rash. Up to half of maternal infections are subclinical despite viremia that may cause devastating fetal infection. Rubella may be isolated from the urine, blood, nasopharynx, and cerebrospinal fluid for up to 2 weeks after rash onset. The diagnosis is usually made, however, with serological analysis. Specific IgM antibody can be detected using enzyme-linked immunoassay from 4 to 5 days after onset of clinical disease, but it can persist for up to 6 weeks after appearance of the rash. Importantly, rubella reinfection can give rise to transient low levels of IgM. Serum IgG antibody titers peak 1 to 2 weeks after rash onset. This rapid antibody response may complicate serodiagnosis unless samples are initially collected within a few days after the onset of the rash. If, for example, the first specimen was obtained 10 days after the rash, detection of IgG antibodies would fail to differentiate between very recent disease and preexisting immunity to rubella. IgG avidity testing is performed concomitant with the serological tests above. High-avidity IgG antibodies indicate an infection at least 2 months in the past. Rubella is one of the most complete teratogens, and sequelae of fetal infection are worst during organogenesis. Pregnant women with rubella infection and a rash during the first 12 weeks of gestation have a fetus with congenital infection in up to 90 percent of cases Udayana University Faculty of Medicine, DME, 2016 51 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases At 13 to 14 weeks’ gestation, this incidence was 54 percent, and by the end of the second trimester, it was 25 percent. Defects are rare after 20 weeks. There is no specific treatment for rubella. Droplet precautions for 7 days after the onset of the rash are recommended. Primary prevention relies on comprehensive vaccination programs. To eradicate rubella and prevent congenital rubella syndrome completely, a comprehensive approach is recommended for immunizing the adult population. MMR vaccine should be offered to nonpregnant women of childbearing age who do not have evidence of immunity whenever they make contact with the health-care system. Vaccination of all susceptible hospital personnel who might be exposed to patients with rubella or who might have contact with pregnant women is important. Rubella vaccination should be avoided 1 month before or during pregnancy because the vaccine contains attenuated live virus. Although there is a small overall theoretical risk of up to 2.6 percent, there is no observed evidence that the vaccine induces malformations. MMR vaccination is not an indication for pregnancy termination. Prenatal serological screening for rubella is indicated for all pregnant women. Women found to be nonimmune should be offered the MMR vaccine postpartum. Cytomegalovirus This ubiquitous DNA herpes virus eventually infects most humans. Cytomegalovirus (CMV) is the most common perinatal infection in the developed world. Specifically, some evidence of fetal infection is found in 0.2 to 2.5 percent of all neonates. The virus is secreted into all body fluids, and person-to-person contact with viral-laden saliva, semen, urine, blood, and nasopharyngeal and cervical secretions can transmit infection. The fetus may become infected by transplacental viremia, or the neonate is infected at delivery or during breast feeding. Primary maternal CMV infection is transmitted to the fetus in approximately 40 percent of cases and can cause severe morbidity. In contrast, recurrent maternal infection infects the fetus in only 0.15 to 1 percent of cases. A review of nine studies of CMV vertical transmission rates reported first-trimester transmission in 36 percent, second-trimester in 40 percent, and third-trimester in 65 percent. Naturally acquired immunity during pregnancy results in a 70-percent risk reduction of congenital CMV infection in future pregnancies. However, as noted earlier, maternal immunity does not prevent recurrences, and maternal antibodies do not prevent fetal infection. Also, some seropositive women can be reinfected with a different viral strain that can cause fetal infection and symptomatic congenital disease. Routine prenatal CMV serological screening is currently not recommended. Pregnant women should be tested for CMV if they present with a mononucleosis-like illness or if congenital infection is suspected based on abnormal sonographic findings. Primary infection is diagnosed using CMV-specific IgG testing of paired acute and convalescent sera. CMV IgM does not accurately reflect timing of seroconversion because IgM antibody levels may be elevated for more than a year. Moreover, CMV IgM may be found with reactivation disease or reinfection with a new strain. Thus, specific CMV IgG avidity testing is valuable in confirming primary CMV infection. High anti-CMV IgG avidity indicates primary maternal infection > 6 months before testing. Finally, viral culture may be useful, although a minimum of 21 days is required before culture findings are considered negative. Udayana University Faculty of Medicine, DME, 2016 52 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases Several fetal abnormalities associated with CMV infection may be seen with sonography, computed tomography, or magnetic resonance imaging. In some cases, they are found at the time of routine prenatal sonographic screening, but in others they are part of a specific evaluation in women with CMV infection. Findings include microcephaly, ventriculomegaly, and cerebral calcifications; ascites, hepatomegaly, splenomegaly, and hyperechoic bowel; hydrops; and oligohydramnios. The management of the immunocompetent pregnant woman with primary or recurrent CMV is limited to symptomatic treatment. If recent primary CMV infection is confirmed, amnionic fluid analysis should be offered. Counseling regarding fetal outcome depends on the gestation age during which primary infection is documented. Even with the high infection rate with primary infection in the first half of pregnancy, most fetuses develop normally. There is no CMV vaccine. Prevention of congenital infection relies on avoiding maternal primary infection, especially in early pregnancy. Basic measures such as good hygiene and hand washing have been promoted, particularly for women with toddlers in day-care settings. Although there may be sexual transmission from infected partners, there are no data on the efficacy of preventive strategies. Hepatitis B Chronic hepatitis B virus (HBV) infection is estimated to affect >350 million people worldwide and represents a significant cause of morbidity and mortality related to cirrhosis and hepatocellular carcinoma. Mother-to-child transmission (MTCT) of HBV remains an important source of incident cases of HBV. Current barriers to eradication of incident HBV infections via MTCT include underutilization of immunoprophylaxis with hepatitis B vaccination and hepatitis B immune globulin in certain endemic regions as well as failure of immunoprophylaxis. Hepatitis B perinatal transmission remains a common mode of viral transmission, especially in highly endemic areas globally.The availability over the past decade of effective oral agents that suppress viral replication has allowed the consideration of thirdtrimester treatment to reduce the risk of this transmission. This is important, particularly in pregnant women with very high viral levels (>108 copies/mL or 2 × 107 IU/mL), in whom the risk is highest, but transmission can occur even at levels >200 000 IU/mL. Treatment decisions necessitate careful discussion of risks and benefits as emerging data suggest some possible effect on bone mineral concentration in tenofovir-exposed pregnant women, which must be balanced by a nearly 10% risk of chronic infection with an incurable virus. Pregnant women with HBV must be monitored for clinical flares, with or without medications, and breastfeeding should be allowed as well. In the absence of HBV immunoprophylaxis, 10 to 20 percent of women positive for HBsAg transmit viral infection to their infant. This rate increases to almost 90 percent if the mother is HBsAg and HBeAg positive. Immunoprophylaxis and hepatitis B vaccine given to infants born to HBV-infected mothers has decreased transmission dramatically and prevented approximately 90 percent of infections. Hepatitis C Udayana University Faculty of Medicine, DME, 2016 53 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases Hepatitis C virus (HCV) is a well known cause of chronic liver disease in adults, but the burden of HCV in pregnant women and children is underappreciated. The leading route of HCV acquisition in children is vertical transmission. Women with chronic HCV infection often have uneventful pregnancies without worsening of liver disease or other maternal or infant adverse effects; some women mayeven have improvement. For example, in a series of 266 pregnant women infected with HCV, elevated serum alanine aminotransferase (ALT) levels were detected in 56% of women at the beginning of pregnancy but only 7% during the third trimester. However, 55% of women returned to elevated ALT levels by 6 months postpartum. Such changes may be due to the significant changes in the maternal immune system during pregnancy. Infants born to women infected with HCV were more likely to be low birth weight, small for gestational age, and require neonatal intensive care and assisted ventilation. In the same cohort, women infected with HCV had an increased risk for gestational diabetes but only when combined with excessive gestational weight gain. There is currently no licensed vaccine for HCV prevention. The chronic HCV infection treatment has traditionally included alpha interferon (standard and pegylated), alone or in combination with ribavirin. This regimen is contraindicated in pregnancy because of the teratogenic potential of ribavirin in animals. Learning task 1. What is IgG avidity ? Who important this result for the treatment scenario ? 2. Describe about indication, side effect, effective dose, contra indication of spiramycin ? 3. How to protect pregnant women from Parvovirus infection ? 4. Describe about MMR vaccination ? 5. How to protect pregnant women from Cytomegalovirus infection ? Self assement 1. Explain how to manage pregnant women with human immunodeficiency virus ? 2. Explain how to manage pregnant women with Epstein-Barr virus ? 3. Explain how to manage pregnant women with herpesviruses 6 and 8 ? 4. Explain how to manage pregnant women with varicella ? 5. Explain how to manage pregnant women with syphilis ? 6. Explain how to manage pregnant women with enteroviruses ? LECTURE 38 MALARIA dr. Susila Utama, SpPD-KPTI Abstract Malaria is caused by infection of red blood cells with protozoan parasites of the genus Plasmodium inoculated into the human host by a feeding female anopheline Udayana University Faculty of Medicine, DME, 2016 54 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases mosquito. The five human Plasmodium species transmitted from person to person are P. falciparum, P. vivax, P. Ovale (two species), P. Malariae and P. Knowlesi. The first symptoms of malaria are nonspecific and similar to those of a minor systemic viral illness. They comprise headache, lassitude, fatigue, abdominal discomfort and muscle and joint aches, usually followed by fever, chills, perspiration, anorexia, vomiting and worsening malaise. Disease progression to severe malaria may take days but can occur within a few hours. Severe malaria usually manifests with one or more of the following: coma (cerebral malaria), metabolic acidosis, severe anaemia, hypoglycaemia, acute renal failure or acute pulmonary oedema. If left untreated, severe malaria is fatal in the majority of cases. All patients with suspected malaria should be treated on the basis of a confirmed diagnosis by microscopy examination or RDT testing of a blood sample. Management of uncomplicated malaria using ACT (Artemisinine Combination Therapy) for 3 days but severe malaria must treated with anti malaria intravenous (artesunate). Learning task 1. Explain clinical symptom and sign of malaria 2. Differentiate between uncomplicated malaria and severe malaria 3. Management uncomplicated malaria and severe malaria Self assessment Case: 1. Male, 23 years old come to internal medicine clinic with fever for 6 days. Fever was intermittenly every 2 days, fever was followed by chills and sweathing. He has history travel to Papua. - How to make diagnosis in this case? - How to manage this case? 2. Female, 34 years old come to emergency room with severe headache and fever for 4 days. Physical examination: icterus +, lien S2. Lab examination Hb 4 g/dL, bil total 4,3 mg/dL and plasmodium falciparum on smear. - What is the assessment? - How to manage this case? LECTURE 39 LEPTOSPIROSIS dr. Agus Somia, SpPD-KPTI Abstract Leptospirosis is a widespread zoonosis caused by pathogenic leptospira spp genus. Transmission of disease to new hosts is facilatated by contact with contaminated urine or water source, because leptospira can penetrate broken skin or muocsal surfaces of new hosts. Infection of new host may be asymptomatic or may be causes acute severe disease: the Weil’s disease ( acute renal failure, haemorrhagic diastesis and jaundice) or severe pilmonary haemorrhagic syndrome. The severity of the disease in human depend on leptospira species, the health and immune status of the patient. The mechanisms by which leptospira cause disease are not well understood. There are factors that role in pathogenesis including: toxin production, entry and invasion to the host, immune Udayana University Faculty of Medicine, DME, 2016 55 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases mechanisms and surface lipoprotein leptospira. These mechanism cause pathological alteration is caharacterizes by the development of vasculitis, endothelial damage, and inflammatory infiltrates composed of monocytic cell, plasma cells, histiocytes, and neutrophils. These pathological alteration can cause multiple hemorrhages and deterioration of organ functions are among the most striking clinical manifestation acute severe leptospirosis Antibiotic therapy of leptospirosis including: mild leptospirosis is treated with doxycycline, ampicillin, or amoxicillin. For severe leptospirosis, intravenous penicillin G has long been the drug of choice, although the third-generation cephalosporins cefotaxime and ceftriaxone have become widely used. Alternative regimens are ampicillin, amoxicillin, or erythromycin. Several other antibiotics may be useful—for example, macrolides, fluoroquinolones, and carbapenems but clinical experience with these agents is more limited. Severe cases of leptospirosis can affect any organ system and can lead to multiorgan failure. Supportive therapy and careful management of renal, hepatic, hematologic, and central nervous system complications are important. Keyword: Leptospirosis, pathogenesis, clinical manifestation Reference: 1. Speelman P. Leptospirosis. In: Kasper DL., Braunwald E., Fauci AS., Hauser SL., Longo DL., Jameson JL. eds. Harrison’s Principles of Internal Medicine. 16th ed. Volume 1. Mc. Grow-Hill companies. 2005. p.988-91 2. Edwards CN. Leptospirosis. In: Cohen J., Powderly W.G., Berkley S.F., Holland S.M., Opal S.M., Callandra T. Infectious disease. Mosby. London. 2004. p. 1669-70. Learning Task: Case 1 A 21-year-old, previously healthy man, a farmer by profession, was brought to the Emergency Room by relatives due to high fever, headache, nausea and vomiting, and constant sleepiness. At admission, he was lethargic and clinically dehydrated. At physical examination, conjunctival congestion and petechia in the soft palate region were observed. Pupils were symmetric and reactive. Sclera: icteric. Axillary temperature was 38.8°C, blood pressure was 130/90 mmHg and heart rate was 100 beats/min. 1. Define and describe others symptoms related to the patients that should be asked to this patient 2. Describe physical examination to support diagnosis of this patient. 3. What is possibly diagnosis of this patient? 4. Describe differential diagnosis of this case 5. Describe laboratory and other examination to support the diagnosis 6. Describe management of this patient 7. Describe how to explain to this patient about prognosis of patient`s disease Self assessment: 1. Explain pathogenesis of:leptospirosis 2. Define clinical spectrum of leptospirosis Udayana University Faculty of Medicine, DME, 2016 56 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases 3. Define signs and symptoms of leptospirosis 4. Define management of leptospirosis 5. Describe about complication of leptospirosis LECTURE 40 SKIN INFECTION dr. Ratih Karna, SpKK ABSTRACT Skin Infection is a very common problem in health care setting. This condition can caused by various agents, including bacteria, virus or fungal group. Skin infection is not always caused by pathogenic agent, but also by normal flora of the skin such as Staphylococcus aureus or Candida sp. Examples of skin infection cause by bacteria are furuncles and erysipelas whereas infection cause by virus including Varicella, Herpes Zoster and Herpes Simpleks. Skin infection occurred not merely by the role of infectious agents, but more likely as an interaction of host, agent and enviromental role. Agent factors consist of the pathogenic or virulence factors of the agent itself. Enviromental factor includes the temperature, moisture, climate and enviromental hygiene and crowd. The most important host factor is the function of the skin as protection barriers. Others includes immunological status of the patient and also the presence of other systemic disease, Skin infections caused by different agent group need to be properly diagnosed and treated with appropiate treatment to avoid serious complications. LEARNING TASK 1. A 50 years old women came to emergency room, complaint arose some blister of her left chest since yesterday. It was painful that make her couldn’t sleep well. Since 1 week ago she felt tired and felt burning sensation of that left chest. She went to cardiogist, the doctor said she was fine. a. What other anamnesis neded to ask to this patient b. What are possible differential diagnosis of this patient c. What is the laboratory examination need to confirm diagnosis d. How is the management of the patient e. What are the complication of this patient SELF ASSESSMENT 1. Explain what we should ask in the anamnesis 2. Explain symptom, sign and what kind of examination do we need for the patient LECTURE 41 CENTRAL NERVOUS SYSTEM INFECTION Prof. Dr. dr. Raka Sudewi, SpS(K) Udayana University Faculty of Medicine, DME, 2016 57 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases LECTURE 42 CHILD IMMUNIZATION dr. W. Gustawan, SpA ABSTRACT Immunization or vaccination is the most effective health program and efficient than other health program in the prevention of an infectious disease. Immunity of the body against the disease is the main purpose of the vaccination. Immunity can be given passive and active. Vaccination and immunization are the example of artificial active immunity in which the vaccine stimulate the body's active to make specific antibodies. The vaccine components consist of viruses and bacteria, both viruses and bacteria attenuated or components of viruses and bacteria. Some examples of vaccine are BCG, DPT, Hepatitis B, Hib, measles, pneumococcus, and others. Immunization is based on the immunization schedule in accordance with the age. Learning Task 1. Please describe about the natural and artificial immunity? 2. Please describe about immunization and vaccination? 3. Please describe about the immunological aspects of the immunization process? 4. Please describe about the aim of immunization? 5. Please describe about Universal Child Immunization program? 6. Please describe about type of immunizations? 7. Please describe about immunization schedule? 8. Please describe about adverse events following immunization? Self Assessment A 2 months old boy came to the clinic to get immunization. The history of his immunization were BCG, Hepatitis B and Polio. There is no fever, cough, and runny nose. 1. What immunization should be obtained by the child at this time? 2. What is the aim of giving each of these immunizations? 3. Please describe about how to give DPT immunization, vaccine doses, and the adverse events following immunization? 4. Please describe about how to give Polio immunization, vaccine doses, and the adverse events following immunization? LECTURE 43 THYPOID FEVER dr. Agus Somia, SpPD-KPTI Abstract Typhoid fever is an acute systemic infection which is caused by Salmonella typhi. S typhi is a gram-negative bacilli , aerobic, and moving with flagellae. S. typhi enters the human body Udayana University Faculty of Medicine, DME, 2016 58 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases form contaminated food, and then penetrate to gut mucosal membranes, continue to gut lymph nodes . S.typhi become reproductive and then from thoracic ducts enters to the blood stream, going to the reticuloendothelial system (first bacteremia), occurs in 24-72 hours after S typhi’s entrance and rarely diagnosed diagnosed because it’s asymptomatic. First bacteremia will soon be ended after this microorganism is not shattered because of fagocytosis, due to protection from Vi cappsule. In this organ of reticuloendothelial system, the microorganism continued to be reproductive. This process lasted in 7 until 10 days. And then the microorganism continue to enter the blood stream and cause the secondary bacteremia. Clinical Findings During prodromal stage, there is increasing malaise, headache, abdominal pain and constipation, while the fever ascends in astepwise. After 7-10 days, the fever reaches a plateau and the patient is much more ill, appearing exhausted and often prostrated. There may be marked abdominal distention, especially early, or “pea soup” diarrhea; marked abdominal distention occurs as well. During the early prodrome, physical sign are few. Later, typhoid tongue, splenomegaly, abdominal distention and tenderness, relative bradicardia appear. Laboratory findings: Typhoid fever is best diagnosed by blood culture, which is positive in the first week of illness in 80% patients who have no taken antimicrobial. Culture of bone marrow occasionally are positive when blood cultures are not. The other laboratory test including: PCR, specific serologic test: widal Management: Fluids and electrolytes should be monitored and replaced. Oral nutrition with a soft digestible diet is preferable in the absence of abdominal distension or ileus. No specific limitations on activity are indicated for patients with typhoid fever. As with most systemic diseases, rest is helpful, but mobility should be maintained if tolerable. The patient should be encouraged to stay home from work until recovery. Several antibiotics including: ampicillin, azithromycin. Chlorampenicol, third generation cephalosporins, and quinolon are effective for treatment. Learning Task: Case 1 A 22-year-old male, with feeling generally unwell with fever, headache, malaise and diarrhea. the onset of fever since 7 days ago. His body temperature was 39 degree celcius, blood pressure 120/80 mmHg, Pulse rate 100 beat per minute. 1. Define and describe others symptoms related to the patients that should be asked to this patient 2. Describe physical examination to support diagnosis of this patient. 3. What is possibly diagnosis of this patient? 4. Describe differential diagnosis of this case 5. Describe laboratory and other examination to support the diagnosis 6. Describe management of this patient 7. Describe how to explain to this patient about prognosis of patient`s disease Self assessment: 1. Explain pathogenesis of Typhoid fever 2. Define signs and symptoms of Typhoid fever 3. Define management of Typhoid fever 4. Describe about complication of Typhoid fever Udayana University Faculty of Medicine, DME, 2016 59 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases LECTURE 44 ACUTE GASTROENTERITIS dr. Yuli Gayatri, SpPD Abstract Acute gastroenteritis is define as the inflammation of the mucus membranes of the gastrointestinal tract and is characterized by diarrhea and/or vomiting. It causes significant mortality in developing countries and significant economic burden to developed countries. Worldwide, gastroenteritis affects 3-5 billion children each year, and accounts for 1.5 to 2.5 million deaths per year or 12% of all deaths among children less than 5 years of age. Viruses are responsible for approximately 70% of episodes of acute gastroenteritis and rotavirus is the one of the best studies of these viruses. In developing countries, enteric bacteria and parasites are more prevalent than viruses and typically peak during the summer months. The most common bacterial causes are Salmonella species, Campylobacter sp, Shigella sp and Yersinia sp. Vibrio cholera remains a major cause of gastroenteritis especially after a disaster where sanitation is compromised. Giardia lamblia, Cryptosporidium sp and Entamoeba histolytica are common protozoal infection. The initial clinical evaluation of the patient should focus on assessing the severity of the illness and the need for rehydration and identifying likely causes on the basis of history and clinical findings. Correcting fluid and electrolyte disturbance take patients who are dehydrated of febrile or have blood or pus in their stool. Oral rehydration therapy is as effective as intravenous therapy in treating mild to moderate dehydration in acute gastroenteritis and is strongly recommended as the first line therapy. Antimicrobial therapy are reliably helpful only for patients with bloody diarrhea (most likely shigellosis), suspected cholera with severe dehydration and serious non-intestinal infections ( e.g., pneumonia). Antimicrobial are to be considered the drugs of choice for empirical treatment of traveler’s diarrhea and community-acquired secretory diarrhea when the pathogen is known. Anti-emetics are not routinely recommended in treating acute gastroenteritis, but often used because vomiting is unpleasant and a distressing symptom which can increase the likelihood or dehydration, electrolyte imbalance, pulmonary aspiration and most importantly the need for intravenous hydration or hospitalization. Prevention including; water, sanitation, hygiene, safe food and immunization can substantially reduce the incidence and severity of the disease. Learning task: A 61-years-old woman with diarrhea 6-8 times per day, for 1 day prior to admission, consistency watery and sometime semisolid, without blood or mucus. He complained with sudden onset of vomiting (more than 10 times/day), abdominal pain, nausea, headache, muscle-ache, fever and chills. She is a foreign traveler. Based on an initial examination, patient was conscious, dry mouth, Blood pressure 90/60 mmHg, body temperature was 38,5 ˚C, increasing bowel sound and acral clamy. 1. Find key words related to this case 2. Describe condition related to key words 3. Define organ system that involved in this condition and find probably cause of the key words 4. Define differential diagnosis and other examinations to support the diagnosis 5. Describe kinds of laboratory examination to diagnose 6. Define management of this case Udayana University Faculty of Medicine, DME, 2016 60 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases 7. Define complication and prognosis 8. Define prevention based on individual, family, and community Self assessment: 1. Describe how do people get acute gastroenteritis 2. Describe symptoms of acute gastroenteritis 3. Describe people at risk for acute gastroenteritis 4. Describe diagnosis of acute gastroenteritis 5. Define management of acute gastroenteritis 6. Define prevention of acute gastroenteritis LECTURE 45 URINARY TRACT INFECTION Dr. dr. Wayan Sudhana, SpPD-KGH LECTURE 46 LOWER RESPIRATORY TRACT INFECTION dr. Made Bagiada, SpPD-KPTI LECTURE 47 TOXOPLASMOSIS dr. Yuli Gayatri, SpPD Abstract Toxoplasmosis is a parasitic infection due to Toxoplasma gondii ( T gondii) an obligate intracellular protozoan parasite. This parasite was identified in 1908 by Nicolle and Manceaux, in North African rodent. Its intermediate hosts could be humans or other warm blooded animals. The infections are reported in approximately half of the world’s population, but most are asymptomatic. The high rates of latent Toxoplasma infection (41.9-72%) were reported in South America and in approximately half of the studies (≥40%) from the Asia continent. Of estimated 750 deaths caused by toxoplasmosis in the United States each year. The contamination of the parasite is generally occurred via consumption of infected food or water or, raw/undercooked contaminated meat; by ingesting oocysts via soil (for example, by way of gardening, handling/eating unwashed vegetables). Infection with T gondii could be transmitted vertically from mother to child, even if a minority of infected individuals worldwide acquires the parasite congenitally. There are four groups of individuals in whom, the diagnosis of toxoplasmosis is most critical: pregnant woman who acquire their infection during gestation, fetuses and newborns who are congenitally infected, immunocompromised patient and those with chorioretinitis. Co-infection with other pathogens in humans infected with HIV -1 may enhance the progression of the disease to AIDS. In concurrence with HIV infection, cerebral toxoplasmosis occurs primarily due to Udayana University Faculty of Medicine, DME, 2016 61 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases reactivation of latent Toxoplasma infection and is one of the most frequent opportunistic infections, particularly in patients with full-blown AIDS. Cerebral Toxoplasmosis is the most common clinical presentation of toxoplasmosis and is one of the most frequent causes of focal intra-cerebral lesions that complicates AIDS. Cerebral toxoplasmosis is undoubtedly a serious life-threatening disease but it is treatable when there is a timely diagnosis and prompt treatment, and there are no other concurrent co-infections. Diagnosis of toxoplasmosis in humans is elaborated using various techniques such as detection of anti-Toxoplasma antibodies, mouse inoculation, histological revelation of tachyzoit in tissue sections or smears of body fluid, but the detection of Toxoplasma gondii DNA by molecular methods has revolutionized prenatal diagnosis of congenital toxoplasmosis including the usefulness of molecular methods. Cerebral toxoplasmosis in HIV/AIDS patients usually presents with focal findings, occurs with CD4 < 200, Ig G Toxoplasma antibody (+). Brain scans called CTs or MRIs demonstrate multiple contrastenhancing ring-like lesions. There are few options other than anti- Toxoplasma regimens used as the first choice initial therapy; 6 weeks with sulfadiazine (1.0-1.5g per oral (PO) every 6 hours with pyrimethamine (100-200mg PO loading dose, then 50 mg PO daily) and folinic acid (10-20 mg PO daily) that can reduced the hemato-toxicities related to pyrimethamine. The other regimens is trimethoprim-sulphamethoxazole (Co-trimoxazole 5/25 mg/kg PO or intravenous (iv) every 12 hours for 4-6 weeks. Several alternative therapies, principally used in patients who are intolerant to this combination, have been reported to be effective, including clindamycin and pyrimethamine or sulfadiazine, clarithromycin and pyrimethamine, or azithromycin and pyrimethamine. Learning task: Case 1: A 41-years-old man with los of consciousness for 5 days prior to admission. He complained with high grade fever since 1 month, headaches, lost of appetite and chronic diarrhea. Lost of body weight about 20 kg in 1 month. He sought treatment from local district hospital doctor, in 2 days admission, such as; dexametasone 10 mg iv every 12 hours, cotrimoxazole 1x 960 mgper oral (PO), paracetamol 3x500 mg PO, ranitidin 1x50 mg iv, antasida 3xCI. He was referred to Sanglah Hospital for intensive treatment, with diagnosis: lost of consciousness probable due to SOL cerebri. Based on an initial examination, patient was unconscious, look pale and severe ill, body temperature was 38,5 ˚C, with oral plaque. 1. Find key words related to this case 2. Describe condition related to key words 3. Define organ system that involved in this condition and find probably cause of the key words 4. Define differential diagnosis and other examinations to support the diagnosis 5. Describe kinds of laboratory or radiology examination to diagnose e.q. serology test, imaging, tissue biopsy etc 6. Define management of this case 7. Define complication and prognosis 8. Define prevention based on individual, family, and community Self assessment: 1. Describe how do people get Toxoplasmosis 2. Describe symptoms of Toxoplasmosis Udayana University Faculty of Medicine, DME, 2016 62 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases 3. 4. 5. 6. 7. 8. Describe people at risk for toxoplasmosis Describe the life-cycle of toxoplasma gondii Describe pathogenesis of toxoplasmosis Describe diagnosis of toxoplasmosis Define management of toxoplasmosis Define prevention of toxoplasmosis LECTURE 48 FILARIASIS dr. Dewi Dian Sukmawati, SpPD ABSTRACT Filariasis is a disease group affecting human and animal, caused by filariae, a nematode (round worm) parasite from Filariidae order. The transmission of filariasis from infected individual to uninfected individual via mosquito bite. Mosquitoes of the genera Aedes, Anopheles, Culex, or Mansonia are the intermediate hosts and vectors of all species that cause lymphatic filariasis. There were hundreds filarial species and fortunately only eight use humans as their definitive host. In Indonesia, there were 241 districs from 26 provinces with endemic filariasis; with national eradication program, the government targeted by the year 2020, Indonesia will be free from elephantiasis. The WHO has identified lymphatic filariasis as the second leading cause of permanent and long term disabilities after leprosy. In lymphatic filariasis, repeated episode of lymphedema and inflammation lead to lymphatic damage, chronic edema and elephantiasis of the leg, arms, scrotum, vulva and breast. Based on the predilection of filarial infestation within human body, filariasis divided into three groups: (1) Lymphatic filariasis, caused by Wucheria brancrofti, Brugia malayi and Brugia timori. These worms occupy the lymphatic system including lymph nodes, in chronic case may lead to syndrome of elephantiasis. (2) Subcutaneous filariasis, caused by Loa loa (eye worm), Mansonella streptocerca, Onchocerca volvulus. These worms occupy subcutaneous layer of the skin at the fat layer. (3) Serous cavity filariasis caused by Mansonella perstans, Mansonella ozzardi. They occupy the serous cavity of abdomen. Diagnosis of filariasis by detection of microfilaria through examination of blood (microfilariae of all species that can cause lymphatic filariasis, Loaiasis (Loa loa), Mansonella ozzardi, Mansonella perstans), urine (chyluria in lymphatic filariasis, in concentrated urine evaluation may revealed microfilaria), skin ( Onchocerca volvulus and M streptocerca infections are diagnosed when microfilariae are detected in multiple skin-snip specimens from different sites located on both sides of the body), eye (microfilariae of O volvulus may be detected in the cornea or anterior chamber of the eye using slit-lamp examination). Imaging study and histology evaluation may be used to demonstrate and monitor lymphatic obstruction. Management of filariasis including antihelmintics (Diethylcarbamazine, ivermectin, suramin, mebendazole, albendazole, flubendazole), surgerical excision can be considered in lymphatic filariasis with large hydrocele and scrotal elephantiasis. LEARNING TASKS Udayana University Faculty of Medicine, DME, 2016 63 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases Case 1 A 32-year-old Indian man presented with tender swelling of the right scrotum after a fall. He was a migrant worker from India who had come to Bali to work as a yoga teacher. Although there was history of a fall, he denied injury to the groin. Clinical examination revealed enlarged lymphnodes inguinal, tender and swollen right scrotum. Eosinophylia was found on complete blood count. Ultrasound of the scrotum was performed and revealed multiple oval cystic structures with multiple internal septa in the paratesticular region, adjacent to the body and tail of the epididymis. Within one of the cysts, numerous short linear echogenic linear structures were seen moving vigorously. A small right hydrocele was also present. Question Case 1 1. What is the clinical diagnosis of this case? 2. What about the management of the patient? (including planning for diagnostic, treatment, monitoring and education) 3. Describe the prevention strategy that available for this case! Case 2 A 42 year old female patient came to outpatient clinic due recurrent fever which lasted 3 -5 days and recurrent for the last 3 weeks. She started to feel painful swelling from her left axillae since the other day. From physical examination revealed lymphadenitis axillae with redness, warm and tender on palpation in surrounding area. Question case 2 1. What is the clinical diagnosis of this case? 2. What evaluation needed for diagnostic work up? 3. How do you manage this case? 4. How about the prognosis? SELF ASSESSMENT 1. Define the filarial life cycle! 2. Describe the process on obtaining the microfilaria identification from blood sample! 3. Differentiate between acute and chronic stage of filariasis (comparison table including duration of infection, clinical manifestation, diagnostic approach, treatment and prognosis) 4. Differentiate between mass treatment and selective treatment for filariasis (indication, duration, type of medication) REFERENCES 1. Knopp S, Steinmann P, Hatz C, Keiser J, Utzinger J. Nematode infections: filariases. Infect Dis Clin North Am. 2012 Jun. 26(2):359-81 2. Kazura J. Guerrant R, Walker DH, Weller PF, eds. Tropical Infectious Diseases: Principles, Pathogens and Practice. Philadelphia, PA: Churchill Livingstone; 1999. Vol 2: 852. 3. Strengthening the assessment of lymphatic filariasis transmission and documenting the achievement of elimination. WHO Geneva 2014 4. Lymphatic filariasis: A handbook of practical entomology for national lymphatic filariasis elimination programmes. WHO Department of control of neglected tropical diseases 2013 Udayana University Faculty of Medicine, DME, 2016 64 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases LECTURE 49 HIV INFECTION Prof. Dr. dr. Tuti Parwati Merati, SpPD, KPTI Abstract Retroviruses are enveloped viruses, with an RNA genome. The name is derived from the fact that the virus particle contains an RNA-dependent DNA Polymerase (Reverse transcriptase). This enzyme converts the RNA genome into DNA, which then integrates into the host chromosomal DNA. The reverse transcriptase is highly error prone and rapid genetic variation is a feature of this group. The most common retrovirus in human is HIV (human immunodeficiency virus). Since 1981, the first cases presented with immune deficiency syndrome were detected in the United State of America. Several years after that, in 1984 it was known that the syndrome was caused by HIV infection. HIV targeted cells who carry CD4 receptor molecule as the main receptor, though other co-receptor is also needed for HIV to infect the cells, such as CCR5 and CXCR4. Transmissions: Commonly through sexual transmission, Blood transfusion, Mother to infant and rarely accidental occupational exposure Primary HIV infection may present with the clinical picture of a febrile illness approximately 2–4 weeks after exposure. The symptoms may include skin rash, myalgia, fatigue, sore throat, diarrhoea, lymphadenopathy, hepatosplenomegaly and, rarely, neurological symptoms. While this seroconversion illness may occur in up to 70–80% of individuals, it is often not viewed as serious or related to HIV infection, due in part to its self-limited course. Primary HIV infection seldom results in presentation to health care settings. In line with the course of time of infection, when the immune system becomes progressively damaged by HIV, reflected by an increased of HIV viral load and a steady decline of the CD4 lymphocyte count to 200 – 350 cells/μL, the patient may develop symptoms that are commonly associated with HIV disease. These include persistent fever, night sweats, significant weight loss, oral thrush, herpes zoster and chronic diarrhoea. A range of opportunistic infection will occur. Thrombocytopenia and lymphopenia may be present on blood testing. It should be noted that any organ system can become involved in opportunistic infections and the clinical presentation of acquired immunodeficiency syndrome (AIDS) is therefore highly variable. Please see WHO Classification for disease staging and also CDC classification of HIV infection based on laboratory examination and the list of diseases referred as AIDS defining illnesses (ADI). So, infection with HIV will covered a very wide range, from asymptomatic to severe clinical manifestation of opportunistic infection. Diagnosis of HIV infection can be made if there are risk factors of HIV infection, clinical manifestation of disease mentioned above, especially in late stage will presented with AIDS defining illness and laboratory test positive for HIV-antibody or any other test confirming HIV infection, such as P24 Ag test and HIV viral load test. Treatment to HIV/AIDS, include treatment to the specific manifestation of opportunistic infection, antiretroviral treatment, supportive treatment, symptomatic drugs, supportive counseling, psychological treatment and counseling to increased adherence. Learning task: A young man aged 35 years-old came to the hospital with difficulty in swallowing, dry mouth and fever. He also had diarrhea since a couple months ago, loose 7 kg of his body weight, Udayana University Faculty of Medicine, DME, 2016 65 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases and feel unwell to work. Because he cannot eat, he become very week and also had a dry cough which made him mostly have to stay in bed. 1. What syndrome do this young man suffering from? 2. On history taking, what information do you want to know from the patient to lead you to a possible working diagnosis? Please explain. 3. What is the diagnosis of this patient? 4. How do you manage this patient? Self assessments: 1. Describe the pathogenesis of immune deficiency in HIV infection. 2. The clinical manifestation of HIV infection is very wide spectrum, from very mild and asymptomatic to a severe- life threatening diseases. How can we make diagnosis of the infection or diseases? LECTURE 50 AVIAN INFLUENZA, SARS dr. Agus Somia, SpPD-KPTI Abstract Bird flu (avian influenza, AI) is an infection caused by the influenza A virus subtype H5N1, which generally attack birds (birds and chickens). Type A influenza viruses are members of the Orthomyxoviridae family. On the surface of the virus type A, there are two glycoproteins: hemagglutinin (H) and neuraminidase (N). Subtypes based on the nature of H (H1 to H16) and N (N1 to N9). The avian influenza virus can survive in water up to 4 days at a temperature of 22 0C and more than 30 days at a temperature of 00C. in poultry feces and body sick poultry, the influenza virus can live long, but died on heating 60 0 C for 30 min, 56 0C for 3 hours and heating to 80 0 C for 1 minute. The virus will die with detergents, disinfectants for example formalin, a liquid containing iodine or 70% alcohol. Mode of transmission: Transmission of the disease to humans can be through: - Animals: direct contact with sick poultry or poultry products were sick. - Environment: air or equipment contaminated with the virus both derived from poultry feces or secretions are attacked AI - Human: very limited and inefficient (found some cases in a group / cluster) Period of communicability: Period of transmission to humans is 1 day before, until 3-5 days after onset of symptoms. In children, the infectious period can be up to 21 days. High risk groups: Group to watch and at high risk of AI infection are: - farm workers / poultry processing (including veterinary / animal husbandry engineer) - Laboratory workers who process the blood sample / patient secretions / poultry infected - The visitors livestock / poultry processing in one last week had contact with poultry (chickens, ducks, birds) sick or died suddenly of unknown causes and or pork as well as raw products in the past 7 days Udayana University Faculty of Medicine, DME, 2016 66 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases - AI patients had contact with confirmation in the last 7 days. Pathogenesis The pathogenesis is determined by the virulence of the virus and the host immune response. Factors affecting virulence include high haemaglutinin solution which is activated by a variety of cellular protease which is a specific substitution in the polymerase basic protein 2 (Glu627lys) which increasing replication. And a sbstitusi in nonstructural protein 1 (Asp92Glu) that confers increased resistance to constraints by interferon and TNF alpha in vitro and extend replication in swine, increasing release of cytokines, especially TNF alpha in macrophag human exposure to the virus. Clinical spectrum The incubation period: 3 days (average 1-7 days) Clinical symptoms vary, not all existing symptoms, can vary from person to person, and tends to quickly deteriorate and develop pneumonia or acute respiratory failure. Clinical symptoms include: high fever (temperature ≥ 380C), cough, runny nose, sore throat, headache, muscle pain, infection of the lining of the eyes, spasms, diarrhea or gastrointestinal disturbances, fatigue. Complication: acute respiratory failure Laboratory: confirmation test: - Culture and identification of influenza A virus subtype H5N1 - RT-PCR testing for H5 Serology: - Test immunofluorescence assay (IFA): antigen (positive) using a monoclonal antibody influenza A subtype H5N1 - Neutralization test: there is an increase in specific antibody titers of influenza A subtype H5N1 4 times, in paired serum neutralization test Radiolography: chest x rays: ARDS Diagnosis : Case definitions suspected cases - someone who has a fever / suhu ≥ 380C accompanied by one or more symptoms: cough, sore throat, colds and shortness of breath, and followed by one or more of the following circumstances: had contact with poultry (chicken, duck, bird) illness or sudden death of unknown cause and the raw products (meat, eggs, poultry manure, etc.) in the last 7 days before onset of symptoms above - live or have ever been in the area of poultry deaths have unusual (in large quantities in a short time), in the last 7 days before onset of symptoms above - had been in contact with patients confirmed AI cases in the last 7 days before the onset of the above symptoms. - had contact with the specimen in the last 7 days before onset of symptoms above (working in the laboratory for AI) - leukopenia - found the H5 antibody titers against the examination HI test using horse erythrocytes or ELISA test for without subtypes of influenza - chest x rays found pneumonia picture that quickly deteriorate in the photo series OR Udayana University Faculty of Medicine, DME, 2016 67 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases The presence of acute respiratory distress syndrome (ARDS) were not found another cause with one more condition below: Leukopenia or relative limfositopeni obtained from counts with or without thrombocytopenia (below normal values) chest film depicts atypical pneumonia or pulmonary infiltrates on both sides of the widening in the photo series The case probabel criteria for suspected cases coupled with one or more of the following circumstances: - found wearing titer antibodies against H5, a minimum of four times, with the examination of HI test using horse erythrocytes or ELISA test - Limited laboratory results positive for influenza H5 (H5 userspecific detection of antibodies in a single serum) using test neutralisasi (sent to a reference laboratory) The cases confirm probabel suspected cases or with one or more of the following circumstances: a. AI virus culture / H5N1 Positive b. PCR AI / H5N1 Positive c. In asssy immunofluorescence test (IFA) antigen (positive) by using monoclonal antibodies AI / H5N1 d. The increase in antibody titer AI / H5N1 Positive konvalescen phase (paired sera) with the neutralization test 4 times the value of the initial (acute phase) Differential diagnosis: - typhoid fever - dengue fever - pulmonary tuberculosis - lung infections caused by bacteria or fungi. Management: - supportive therapy: oxygen, fluid therapy, nutrition - Antiviral given as soon as possible (48 hours). - Body weight > 40 Kg: Oseltamivir 2 X 75 mg per day for 5 days References 1. Ministry of Health. Guidelines for Management of Avian Influenza in Health Care Facilities. Jakarta. 2006 - Learning Task: Male 45 years, previously healthy, broilers collectors work, was escorted to the emergency room, complaining of fever, cough, and shortness of breath since 3 days.. 1 month ago history of some chickens on the farm, many died. on physical examination found awareness of apathy, Blood pressure: 90/60, respiratory rate: 40 time per minute, pulse rate: 120 time per minute, axillary temperature: 39oC. On thorax examination found: ronchy a both lung. 1. Define and describe others symptoms related to the patients that should be asked to this patient 2. Describe physical examination to support diagnosis of this patient. 3. What is possibly diagnosis of this patient? 4. Describe differential diagnosis of this case 5. Describe laboratory and other examination to support the diagnosis 6. Describe management of this patient 7. Describe how to explain to family this patient about prognosis of patient`s disease 8. Describe how to referral of this patient Udayana University Faculty of Medicine, DME, 2016 68 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases Self assessment: 1. Explain pathogenesis of: avian influenza 2. Define clinical spectrum of avian influenza 3. Define signs and symptoms of avian influenza 4. Define management of avian influenza 5. Describe about complication of avian influenza 6. Define prognosis of avian influenza LECTURE 51 SEVERE ACUTE RESPIRATORY SYNDROME (SARS) dr. Agus Somia, SpPD-KPTI Abstract Severe acute respiratory syndrome (SARS) is a serious form of pneumonia. It is caused by a virus that was first identified in 2003. Infection with the SARS virus causes acute respiratory distress (severe breathing difficulty) and sometimes death. Causes: SARS is caused by a member of the coronavirus family of viruses (the same family that can cause the common cold). It is believed the 2003 epidemic started when the virus spread from small mammals in China. Transmission: When someone with SARS coughs or sneezes, infected droplets spray into the air. The SARS virus may live on hands, tissues, and other surfaces for up to 6 hours in these droplets and up to 3 hours after the droplets have dried. While the spread of droplets through close contact caused most of the early SARS cases, SARS might also spread by hands and other objects the droplets has touched. Airborne transmission is a real possibility in some cases. Live virus has even been found in the stool of people with SARS, where it has been shown to live for up to 4 days. The virus may be able to live for months or years when the temperature is below freezing. With other coronaviruses, becoming infected and then getting sick again (re-infection) is common. This may also be the case with SARS. Clinical manifestation: Symptoms usually occur about 2 to 10 days after coming in contact with the virus. In some cases, SARS started sooner or later after first contact. People with active symptoms of illness are contagious. But it is not known for how long a person may be contagious before or after symptoms appear. The main symptoms are: cough,difficulty breathing, fever greater than 100.4°F (38.0°C) and other breathing symptoms Laboratory for identify the virus that causes SARS include: Antibody tests for SARS, direct isolation of the SARS virus and rapid polymerase chain reaction (PCR) test for SARS virus Radiolography: chest x rays found pneumonia and ARDS picture Diagnosis: based on clinical manifestation and radiography finding Management: supportive treatment, antiviral (ribavirin no strong evidence) and general precaution for infection control Learning Task Case Udayana University Faculty of Medicine, DME, 2016 69 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases Male 45 years, previously healthy, businessman , was escorted to the emergency room, complaining of fever, runny nose, sneezing and cough since 7 days ago. He feel shortness of breath getting worse since 3 days. He has history going to Hongkong 10 days ago and transit at Singapore. On physical examination found awareness of apathy, Blood pressure: 90/60, respiratory rate: 40 time per minute, pulse rate: 120 time per minute, axillary temperature: 38.7oC. On thorax examination found: ronchy a both lung. 1. Define and describe others symptoms related to the patients that should be asked to this patient 2. Describe physical examination to support diagnosis of this patient. 3. What is possibly diagnosis of this patient? 4. Describe differential diagnosis of this case 5. Describe laboratory and other examination to support the diagnosis 6. Describe management of this patient 7. Describe how to explain to family this patient about prognosis of patient`s disease 8. Describe how to referral of this patient Self assessment: 1. Explain pathogenesis of SARS CoV infection. 2. Define clinical spectrum of SARS CoV infection. 3. Define signs and symptoms of SARS CoV infection. 4. Define management of SARS CoV infection. 5. Describe about complication of SARS CoV infection. 6. Define prognosis of SARS CoV infection. LECTURE 52 PAROTITIS dr. Dewi Dian Sukmawati, SpPD ABSTRACT The parotid glands are small exocrine glands that rarely function abnormally, mostly they function perfectly normal throughout life. Dry mouth, drooling, swelling, and pain are essentially the only symptoms caused by dysfunction of the salivary glands. Inflammatory swelling of the glands may present a serious diagnostic challenge. Parotitis presents in many forms and the symptoms vary from modest to prostrating. There are frequent contradictions in the classification, etiology, and treatment of the disorders. A pure viral or bacterial infection, an autoimmune inflammation, or a combination of these can be the etiology. In unilateral parotitis, consider a bacterial infection, local obstruction, or malignancy. High fevers and a toxic appearance can develop in bacterial parotitis and should be considered in the elderly, dehydrated, and malnourished patients. History and physical should lead towards a cause. Biopsy may be necessary, especially if facial nerve paralysis also present. Parotitis epidemica (mumps)’s etiology in children usually due to viral infection from a paramyxovirus. The mumps virus replicates in the upper respiratory tract and spreads through direct contact with respiratory secretions or saliva or through fomites. The risk of Udayana University Faculty of Medicine, DME, 2016 70 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases spreading the virus increases the longer and the closer the contact a person has with someone who has mumps. Some complications of mumps are known to occur more frequently among adults than children. Death from mumps is exceedingly rare. Mumps can be prevented by administration of vaccine called MMR. LEARNING TASKS Case A 25 year old pregnant woman came to outpatient clinic due to 3 days fever. In the last two days she noticed pain, tenderness and swelling is first visible in front of the lower part of the ear. It then extends downward and forward her cheek and jaw area. Three weeks before, one of her niece which was 5 year old was suffered from the same condition. Some of the children around the neighborhood within this past one month also ever suffered the same complain Question 1. What is likely the clinical diagnosis for this case? 2. How do you manage this case? (including diagnostic, treatment, monitoring and education) 3. What condition can be present as a complication for this case? Self assessment 1. What are the possible etiologies of parotitis? 2. How can we differentiate between viral, bacterial, autoimmune or malignancy etiology? 3. How about the vaccination strategy for mumps? REFERENCES 1. McLean HQ, Fiebelkorn AP, Temte JL, et al. Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2013 Jun 14. 62:1-34 2. Mumps; epidemic parotitis. In Oxford text book of medicine: Infection. Oxford university press 2012 3. Kasper DL; Braunwald E; Fauci AS; Hauser SL; Longo DL; Jameson JL; Isselbacher KJ; Eds. (2011). "194. Mumps".Harrison's Principles of Internal Medicine (18th ed.). McGraw-Hill Professional LECTURE 53 BACTEREMIA, SEPSIS dr. Susila Utama, SpPD-KPTI Abstract Sepsis is defined as a known or suspected infection plus systemic manifestations of infections (eg, traditional systemic inflammatory response syndrome criteria—tachy-cardia, tachypnea, white blood count changes, and fever/hypothermia as well as other metabolic perturbations or organ dysfunctions). Severe sepsis is defined as sepsis plus infectioninduced organ dysfunction or infection-induced acute tissue hypoperfusion. Bacteriemia is Udayana University Faculty of Medicine, DME, 2016 71 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases the presence of viable bacteria in the blood. Early diagnosis, early antibiotic administration, and adequate fluid resuscitation are key in decreasing sepsis morbidity and mortality. Learning task 1. Explain definition of bacteriemia, sepsis, severe sepsis and septic shock 2. How to manage sepsis, severe sepsis and septic shock Self assessment Male, 69 years old was admitted in intensive care unit with severe pneumonia, impending respiratory failure, blood pressure 80/60, pulse 124 irreguler per minute and respiratory 29 perminute, temperature 35,2 o Celcius. Physical examination: rales on paracardial of the right lung. Urine was 25 cc for 4 hours. Laboratory exam: WBC 23 and metabolic acidosis on blood gas analysis - What is the diagnosis of this case? - How to manage this case? LECTURE 54 RABIES dr. Susila Utama, SpPD-KPTI Abstract Rabies, present on all continents and endemic in most African and Asian countries, is a fatal zoonotic viral disease,transmitted to humans through contact (mainly bites and scratches) with infected animals, both domestic and wild. Rabies is estimated to cause at least 55 000 deaths per year worldwide, about 56%of which occur in Asia and 4 %in Africa, particularly in rural areas on both continents. The risk of infection depends on the severity of the wound, the site of the wound in relation to its nerve supply and its distance from the brain, the amount and strain of virus introduced. The initial symptoms of rabies resemble those of other systemic viral infections, including fever, headache and generally feeling unwell. There may be discomfort or paresthesia at the site of exposure (bite), followed by symptoms of cerebral dysfunction, anxiety, confusion, agitation, progressing to delirium, abnormal behaviour, hallucinations, and insomnia i.e. furious (or encephalitic) rabies. Fever is common and signs of autonomic dysfunction, including hypersalivation, sweating, piloerection, and priapism (in males) may be present. About 50% to 80% of patients develop hydrophobia, which is a characteristic manifestation of rabies. Patients may initially experience pain in the throat or difficulty swallowing. On attempting to swallow, they experience contractions of the diaphragm and other inspiratory muscles, which last about 5 to 15 seconds. Subsequently, the sight, sound, or even mention of water (or any liquids) may trigger the spasms. A draft of air on the skin may have the same effect (ie, aerophobia). The disease may progress through paralysis, coma, multiple organ failure, and eventually death. Viral encephalitis caused by other viruses is generally associated with earlier impairment of consciousness compared with rabies, with less prominent early evidence of brainstem involvement. Occasionally the presentation is with sudden death. Neurological symptoms occur later in the disease process. The acute period of disease typically ends after 2 to 10 days. Once clinical signs of rabies appear, the disease is nearly always fatal, and treatment is typically supportive. Udayana University Faculty of Medicine, DME, 2016 72 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases There is no specific treatment for rabies, which is a fatal disease. Prevention of rabies were pre and post exposure prophylaxis, clean the wound was most important followed by vaccine and immunoglobulin. Learning task 1. Explain the symptom and sign of rabies 2. Explain rabies prevention by pre and pro exposure prophylaxis Self assessment Male, 13 years old was bite by dog 2 hours ago, so he come to polyclinic for rabies vaccination. Please explain to the patient, what must we do? Is he need vaccination? LECTURE 55 TETANUS dr. Yuli Gayatri, SpPD Abstract Tetanus is a vaccine preventable disease that yearly cause a total of 309.000 deaths. The global incidence of tetanus has been estimated at approximately one million cases annually mostly in underdeveloped countries. Mortality rates from tetanus very greatly across the world, depending on access to the healthcare, and approach 100% in the absence of medical treatment . Clostridium tetani is an anaerobic bacillus, whose spores survive in soil and cause infection by contaminating wounds. Tetanus toxin, the product of Clostridium tetani, is the cause of tetanus symptoms. Tetanus is taken up into terminals of lower motor neuron and transported axonally to the spinal cord and /or brainstem. Here toxin moves trans-synaptically into inhibitory nerve terminals, where vesicular release of inhibitory neurotransmitter becomes blocked, leading to disinhibition of lower motor neurons. Muscle rigidity and spasms ensue, often manifesting as trismus/lockjaw, dysphagia, opistotonus, or rigidity and spams of respiratory, laryngeal and abdominal muscles, which may cause respiratory failure. There is no diagnostic laboratory test for tetanus; the diagnosis is entirely clinical. C tetani is recovered from wounds is only about 30% of cases and the organism is sometimes isolated from patients who do not have tetanus. Serological results obtained before TIG is administered can support susceptibility if they demonstrate very low or undetectable anti-tetanus antibody levels. Acute treatment of tetanus is based on wound cleaning and antibiotic eradication of Clostridium tetani, e.g. with intravenous metronidazole 500 mg three times daily or penicillin 100.000-200.000 IU/kg/day, treatment is continued for seven to ten days and the administration of tetanus toxoid and/or tetanus immunoglobulin. Learning Task: 1. Describe how do people get tetanus 2. Describe symptoms of tetanus 3. Describe people at risk for tetanus 4. Describe diagnosis of tetanus 5. Define management of tetanus 6. Define prevention of tetanus Udayana University Faculty of Medicine, DME, 2016 73 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases ~ CURRICULUM MAP ~ Smstr Program or curriculum blocks 10 Senior Clerkship 9 Senior Clerkship 8 Senior clerksh ip 7 Medical Emergency (3 weeks) Special Topic: -Travel medicine (2 weeks) Elective Study III (6 weeks) Clinic Orientation (Clerkship) (6 weeks) 6 BCS (1 weeks) The Respiratory System and Disorders (4 weeks) The Cardiovascular System and Disorders (4 weeks) The Urinary System and Disorders (3 weeks) The Reproductive System and Disorders (3 weeks) BCS (1 weeks) Alimentary & hepatobiliary systems & disorders (4 Weeks) BCS (1 weeks) The Endocrine System, Metabolism and Disorders (4 weeks) BCS (1 weeks) Clinical Nutrition and Disorders (2 weeks) BCS (1 weeks) BCS (1 weeks) Musculoskeletal system & connective tissue disorders (4 weeks) Neuroscience and neurological disorders (4 weeks) Behavior Change and disorders (4 weeks) BCS (1 weeks) Hematologic system & disorders & clinical oncology (4 weeks) BCS (1 weeks) Immune system & disorders (2 weeks) BCS(1 weeks) Infection & infectious diseases (5 weeks) BCS (1 weeks) The skin & hearing system & disorders (3 weeks) BCS (1 weeks) Medical Professionalism (2 weeks) BCS(1 weeks) Evidence-based Medical Practice (2 weeks) BCS (1 weeks) Health Systembased Practice (3 weeks) BCS(1 weeks) Community-based practice (4 weeks) - BCS (1 weeks) Studium Generale and Humaniora (3 weeks) Medical communication (3 weeks) BCS (1 weeks) The cell as biochemical machinery (3 weeks) Growth & development (4 weeks) BCS (1 weeks) BCS(1 weeks) BCS: (1 weeks) BCS (1 weeks) Elective Study II (1 weeks) 5 4 3 2 1 BCS (1 weeks) Special Topic : - Palliative medicine -Compleme ntary & Alternative Medicine - Forensic (3 weeks) Elective Study II (1 weeks) Special Topic - Ergonomi - Geriatri (2 weeks) Elective Study I (2 weeks) The Visual system & disorders (2 weeks) Pendidikan Pancasila & Kewarganegaraan (3 weeks) Udayana University Faculty of Medicine, DME, 2016 74 Study Guide Basic Microbiology, Parasitology, Infection and Infectious Diseases REFERENCES 1. Spicer WJ. (200): Clinical Bacteriology, Mycology, and Parasitology, An Illustrated Colour Text. Churchill Livingstone, 14-19. 2. Clinical Bacteriology, Mycology and Parasitology : An Illustrated Colour Text. W. John Spicer. Churchill-Livingstone 3. Brooks et al. pathogenesis and Control of Viral Diseases. In: Lange Medical Microbiology. 23rd ed. McGraw Hill. International Ed. 2004. p. 394 – 413.(Principles of Viral Infection) 4. Levinson et al. Lange Medical Microbiology & immunology. Examination & Board review. 8th ed. McGraw Hill. International Ed. 2004. p. 186 – 220, 259-269, 244250.(Principles of Viral Infection) 5. Roitt. I., Brostoff.J., Male. D. Immunology 6. Durack DT, Whitley RJ, and Scheld WM. Introduction: Approach to the Patient with Central nervous System Infection. In : Scheld WM, Whitley RJ, Durack DT, (eds). Infections of The Central Nervous System. Raven Press. New York. 1991 p. 1-4. 7. Victor M and ropper AH. Infections of the Nervous System (Bacterial, Fungal, spirochetal, Parasitic) and Sarcoid. In: Adams and Victors’ principles of the Neurology. 7th ed. McGraw-Hill. New York/Toronto. P. 734-780. 8. Ottesen EA. Filariasis.in Powderly WG. (ed). Infectious Diseases. 2nd ed. P.160713. 9. Ringsrud KM, Linne JJ. Urinalysis and Body Fluids A Colortext and Atlas. 1st ed. Mosby. St. Louis/ Toronto. 1995. p. 95-206. 10. Burtis CA. Tietz Fundamentals of Clinical Chemistry. 4th ed. WB Saunders Company. Philadelphia/ Tokyo. 1996. p. 558-561. 11. Simmons A. Statland BE. Hematology A combined Theoritical and technical Approach. 2nd ed. Buuterworth-Heinemann. Boston/ Singapore. 1997. p. 129-142. 12. Stites DP, Terr AI, Parslow TG. Medical Immunology. 9th ed. Prentice-Hall International. 1997. p. 264-269. 13. Kasper DL, Fauci AS, Longo DL, Braunwald E, et al. Harrison’s Principles of Internal Medicine. 16th ed. Vol 1. McGraw-Hill. New York/ Toronto. 2005. p. 981-1103. 14. Sutton D. Radiology and Imaging for Medical Students. Churchill Livingstone. 7 th ed. 1998. 15. Grainger RG and Allison DJ. Diagnostic Radiology. Churchill Livingstone. 2 nd ed. 1993. 16. McAdam AJ and Kumar S. Infectious Diseases in Kumar V, Contran RS and Robbins SL, Robbins Basic Pathology. P. 344-398. 17. Andrews. Diseases of The Skin. 9thed. 18. Bryceson A. Leprosy. 3rded. 19. King & Nicole. Sexually Transmitted Diseases. 2003 20. Holmes KK, Spiring PF, Mirdh P. Sexually Transmitted Diseases. 3rd ed. McGrawHill. 1999. 21. McMillan A, Young H, Ogilvie MM, Scott GR. Clinical Practice in Sexually Transmissible Infection. Saunders. 2002. 22. Braunwald’s Heart Disease. Subacute bacterial endocarditis. Udayana University Faculty of Medicine, DME, 2016 75