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Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
Infectious disease of pathology
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Infectious disease of pathology

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Infectious Disease of Pathology

Infectious Disease of Pathology

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  • 1. INFECTIOUS DISEASE OF PATHOLOGY (Part-1) Dr.Naila Awal (Postgraduate student)
  • 2. Categories of infectious agents • • • • • • • Prion Viruses Bacteria Fungi Protozoa Helminths Ectoparasites
  • 3. PRION • Definition- Infectious particle composed of protein Definition (prp) • DiseasesHuman 1) kuru 2)Creutzfeldt- Jackob Disease (CJD) 3)Variant CJD AnimalBovine spongiform encephalopathy TransmissionIartogenically Surgery Organ transplantation Blood transfusion
  • 4. Pathogenesis- Prp normally found in neuron. Disease occur when prp conformational change protease resistant prp I Normal Protease I Abnormal Sensitive prp ------ prp ---Neuronal damage Inactivation- By protein and lipid disrupting agent such as Phenol Ether NaOH Hypochlorite
  • 5. New and Emerging infectious diseases • DefinitionNewly identified & previously unknown agent that appeared in human population & causes public health problem is known as emerging infectious disease.
  • 6. These includes1) Disease caused by newly developed strains/ microorganismEx- MDR-TB XDR-TB MRSA Chloroquine resistant malaria 2) Disease caused by pathogens, endemic in other species (birds) that recently entered into human populationEx-HIV, SARS 3) Disease caused by pathogens that have been present in human population but show recent incidence Ex-Dengue fever
  • 7. Factors contributing to emergence— 1)Enviornment– Climate & changing ecosystem Urbanization & deforestation 2)International travel 3)Breakdown of public health measures (war, overcrowding)
  • 8. Bioterrorism • Definition- Intentional release of viable bacteria, virus & toxin in order to harm people, animal/plant.
  • 9. • Category A -->Highest risk -->Easily disseminated/ transmitted from person to person -->High mortality • Anthrax- Bacillus anthracis • Botulism- Clostridium botulinum • Plague- Yersinia pestis • Small pox- Variola major virus • Viral hemorrhagic fever- Filovirus
  • 10. • Category B Moderately easy to disseminated Moderate morbidity but low mortality • Brucellosis- Brucella • Melioidosis- Burkholderia pseudomallei • Glanders- Mallei • Staphylococcal enterotoxin B • Epsilon toxin of Clost. perfringes • Food safety threats Salmonella, Shigella, E.coli • Water safety threatsV.cholerae, Cryptosporidium pavum
  • 11. • Category C • Emerging pathogensNipah virus Hanta virus
  • 12. Transmission & dissemination of microbes • ROUTE OF ENTRY • SKINNatural barrier1)Dense keratinized layer of skin 2)Low pH 3)Fatty acid- the growth of micro organism
  • 13. • Unbroken skin- • Penetrate through broken skin • I/V catheter • Schistosoma larva Release collagenase, elastase dissolve ECM penetrate swimmers skin • Superficial prick-Fungus • Wound-Staph • Burn-Pseudomonas • Bacteremia
  • 14. • Needle stick • Insect bite • Animal bite • HBV,HCV,HIV • Tick transmitRickettsiae-RMSF Brucella-Lyme disease • Flea--Y.pestis- plague • Mosquito-Malaria, Filaria • Sand fly- L.donavanileishmaniasis • Dog-Rabies
  • 15. • GIT • Natural defense1)Mucosal covering of intestinal epithelium 2) Mucosal antimicrobial agent-defensin 3)Lytic pancreatic enzyme & bile detergent 4)Normal flora 5)Secretory IgA
  • 16. 1)Enteropathogenic bacteria1)Staphgrow in contaminated food release enterotoxin food poisoning without multiplication in the gut. 2)V. cholerae, ETEC multiply inside the mucus layer covering gut epithelium exotoxin release watery diarrhea. 3)Salmoella,Shigella,Champylobacterinvade & damage intestinal mucosa & lamina propria ulceration, inflammation & hemorrhage dysentery. 4)S.typhisystemic infection.
  • 17. • FungusCandidal infection- mainly in immunocompromised person. • Intestinal protozoaGiardia lamblia Entamoeba histolytica Cryptosporidia
  • 18. • Intestinal helminthsAscaris lumbricoides gut obstruction/invade & damage the bile duct Hookworm IDA Diphyllobothrium latum vit B12 depletionmegaloblastic anemia T.Solium larva- encyst in muscle E. Granulosus larva-encyst in lung, liver
  • 19. • Respiratory tract• Natural defense1)Mucocilliary apparatus large particles are trapped. 2)Alveolar macrophage & neutrophil particle<5micro meter alveoli phagocytosed by alveolar macrophage & neutrophil.
  • 20. Mechanism1)Micro organism attached to lower respiratory tract & laryngeal epithelium ExampleInfluenza virus-has 2 cell surface proteins- – Hemagglutinin (function at the beginning of the infection) -Neuraminidase-(function at the end of the infection. They degrade the protective layer of mucus in respiratory tract)
  • 21. Influenza virus Hemagglutinin Neuraminidase Bind with epithelial surface receptor 1)Cleave the sialic acid allow the virus to release from host cell Host cell engulf the virus Replicate within the cell 2) the viscosity of mucus facilitate viral transit within respiratory tract
  • 22. 2) Impaired ciliary activityExample• H. Influenzae & B. pertussis- release toxin ciliary paralysis. • Mycoplasma pneumoniae- produce ciliostatic substances • Smoker/people with cystic fibrosis-chronic damage to mucociliary apparatus
  • 23. 3)Some respiratory pathogen avoid phagocytosis/destruction after phagocytosis Example• M tuberculosis- escape killing within phagolysosome of macrophage 4)Opportunistic fungus- infect when CMI /when leukocyte are in number. ExamplePneumocystis jirovechi in AIDS Aspergillus followed by chemotherapy.
  • 24. • Urinary tract • Natural defense Regular flushing of urinary tract by urine
  • 25. Spread & dissemination of microbes Some micro-organism proliferate locally at the site of infection & others spread to distant site vialymphatic's, blood & nerve. • Local- a) Confined to lumen of hollow visceraV. cholerae. b) Adhere /proliferate in/on epithelial cell- HPV/dermatophytes.
  • 26. Invasive• LymphaticsEx- Staphylococcus-localized abscess/furuncle through lymphatic  drain into regional lymph node sometimes bacteremia & colonize to distant organ. • Blood-Most of bacteria & fungus, Virus- HBV, Polio Protozoa- African trypanosoma All helminths. WBC- MTB,LD, Toxoplasma, HIV, Herpes RBC- Plasmodium, Babesia • Nerve- Polio virus
  • 27. Placental-fetal route• BacteriaMycoplasma placentitis premature delivery/still birth. T.Pallidum2nd trimester osteochondritis, periostitis leads to multiple bony lesion. • VirusRubella1st trimester-Congenital heart disease, Cataract, Deafness. 3rd trimester-Little damage
  • 28. • Infection during passage of birth canalRickettsia/Chlamydia-Conjuctivitis • Milk- CMV,HBV,HTLV-1
  • 29. Release of microbes from the body It depends on the location of infection. Transmission from person-person• Respiratory route- Virus & bacteria. • Saliva- EBV, CMV, Mumps • Feco-oral route- HAV, HEV , Rota virus, Hookworm, Schistosomes • Blood & blood product- HBV, HCV,HIV • Sexual transmission
  • 30. • Transmission from animal-human1) Direct contact / Consumption of animal fat Ex- Bacillus anthracis. 2) Indirectly via invertebrate host. Ex- Malaria – by mosquito.
  • 31. Sexually Transmitted Infection • Definition- Infection that are transmitted through sexual route. • High risk group1)Adolescent 2)Homosexual men 3)Illegal drug abuser • Site- Initial siteVagina Rectum Urethra Oropharynx
  • 32. General featuresInfection with 1 STI associate organism the risk for additional STI Ex- N. Gonorrhea/ Chlamydia trachomatis epithelial injury local tissue damage chance of co-infection with the other & also the risk of HIV infection. . STI can spread by vertical transmission & causes severe damage to fetus/ child Ex- Chlamydia trachomatis Conjunctivitis Syphilis Miscarriage
  • 33. Examples of STI • Bacteria • • • • • Neisseria gonorrhoeae Treponema pallidum Haemophilus ducreyi Klebsiella granulomatis Chlamydia trachomatis • Ureaplasma urealyticum • • • • • Gonorrhea Syphilis Chancroid Granuloma inguinale Lymphogranuloma venereum • Urethritis
  • 34. • Virus • • • • • • HSV HBV HPV HIV Protozoa Trichomonas vaginalis • • • • Herpes Hepatitis Condyloma acuminatum AIDS • Urethritis • Vaginitis
  • 35. Nosocomial Infection • Definition These are hospital acquired infection which develops 48hrs after hospitalization /within 48 hrs after release from hospital. Source 1)Hands of health worker 2)Contaminated surface 3)Used equipment & instrument 4)Blood transfusion 5)Organ transplantation
  • 36. Organism causing Nosocomial Infection • Bacteria• Gram positive • • • • • • Gram negative • Pseudomonas • Proteus • E coli Staph aureus MRSA,VRSA Staph epidermidis Strep pneumoniae Clostridium tetani
  • 37. • Virus • Fungi • Parasite • HBV,HCV,HDV • HIV, HSV,CMV • Candida • Pneumocystis jiroveci • Toxoplasma
  • 38. Risk factor• • • • • • Long time hospital stay Mechanical ventilation I/V catheter Use of indwelling catheter Overdose of antibiotic Failure of health care worker to wash hand.
  • 39. • Prevention 1) Frequent hand washing can transmission of MRSA & VRE. 2) Proper sterilization & disinfection of inanimate object of the hospital. 3) Proper disposal of hospital waste. 4) Rational use of antibiotics. 5)Personal hygiene of patient, attendants, doctor & medical stuff. 6) Detection of proper carrier & proper diagnosis.
  • 40. Host defense against infection • 1) Innate immunitya) Intact skinSebaceous gland--> contain fatty acid antibacterial & antifungal Low pH- antimicrobial. b) Mucous membraneMucociliary apparatus- prevent the entry of microbes through URT Lysozyme in tear & mucus- degrade peptidoglycan layer of bacterial cell wall protect from infection.
  • 41. c) Cellular componentMacrophage, neutrophil phagocytose the microbes. N-K cellproduce toxic substances perforin destroy microbes. d) Soluble componentComplement activation-->formation of MAC destroy cellular Ag. IFNα, IFNβ –released by virus infected cell this IFN replication of viruses. (that’s why viral infection are self limiting)
  • 42. • 2) Acquired immunity- develops after exposure to microbes. They are B & T lymphocyte. Ex- Measles virus enters into the body Ab production Ab binds with measles virus Virus eliminated Provides specific immunity
  • 43. How micro-organism causes diseaes • By 3 mechanisms1)They can directly enter into host cell causes cell death. 2)They may-release toxins kill the cell 3)They may-release enzymes degrade tissue components/damage blood vessel ischemic necrosis. 4)They induce host cell responses causes additional damage.
  • 44. Mechanism of viral injury Virus can directly damage the host cell by entering & replicating within it. • Virus has a affinity for specific body tissue which is determined by – 1)Presence of receptor on host cellExgp120 of HIV binds with CD4 on Tcell CXC R4(T cell) CCR5(macrophage) gp350 of EBV binds with CR2/CD21 on B cell
  • 45. 2) Cellular transcription factor that recognize viral enhancer & promoter sequence Ex- JC virus causes leuko encephalopathy, replicate specially in oligodendroglia in CNS. (B/c enhancer & promoter sequence regulating viral genes are active in glial cell). 3) Physical barrierEx- Entero virus replicate in intestine b/c they can resist inactivation by acid, bile & digestive enzyme. 4)TemparatureEx- Rhinovirus infect only within URT b/c they replicate at lower temperature of URT.
  • 46. Virus can damage the host cell by a number of mechanism• 1) Direct cytopathic effect- Virus can kill the cell directly bya) Prevent the synthesis of host macromolecules (DNA,RNA/protein) Ex-Polio virus- inactivate cap binding protein which is essential for translation of host cell mRNA. b) Producing degradative enzyme & toxic proteins Ex- HSV-Produce protein that synthesis of cellular DNA & mRNA & other proteins that degrade host DNA. c) Inducing apoptosis by producing pro-apoptic protein Ex- HIV vrp protein.
  • 47. 2)Anti viral immune response• Viral protein on the surface of host cell may be recognized by immune system & lymphocyte may attack the virus infected cell. Ex- In HBV infection, acute liver failure is caused by cytotoxic T cell mediated destruction of infected hepatocytes. 3)Transformation of infected cells--> benign/ malignant neoplasm • Oncogenic virus stimulate cell growth & survival by following M/AExpression of virus encoded oncogene Anti-apoptic strategies Insertional mutagenesis
  • 48. Mechanism of bacterial injury • 1) Adherence to the host cell surfacea) Adhesin - is present in bacterial cell surface. Through this they bind to host cell/ECM. Ex- Strep. pyogens adhere to host tissue by protein F & teichoic acid. b) Pili Ex- E.Coli through P pili bind with gal-gal moiety of uroepithelium. c) Glycocalyx Ex-Stap. epidermidis/ Strep. viridians bind with heart valve.
  • 49. • 2)Virulence of intracellular bacteria• Facultative intracellular bacteria infect  -->Epithelial cell (Shigella, ETEC) -->Macrophage (MTB,ML) -->Both (S. typhi) • Growth of bacteria in cell may allow the bacteria to escape the immune system /facilitate the spread. Ex- MTB macrophage lung to other site.
  • 50. Bacteria have a number of mechanism to enter into the cella) Bacteria is coated with Ab/ complement  phagocytosed by macrophage. • Ex-MTB activate alternative pathway of complement opsonization with C3b C3b coated MTB bind with CR3 on macrophage endocytosis into macrophage. b) Gm- bacteria use complex secretion system to enter into epithelial cell. • This system consists of needle like structure form pore inside host cell membrane inject protein rearrangement of cell cytoskeleton bacteria entry. • Ex- L. monocytogenes.
  • 51. c) Effect of bacteria inside the host cella) b) Shigella, E. coli- host protein synthesis within 6 hours host cell lysis. Within macrophage most bacteria killed when phagosome fuse with lysosome & form phagolysosome. But certain bacteria evade this defense. Ex- MTB- block the fusion of phagosome with lysosome unchecked MTB proliferation within macrophage. L. Monocytogenes- produce pore forming protein-listeriolysin O & 2 phospholipase degrade phagosome membrane bacteria escape into cytoplasm.
  • 52. 3) Toxin production• A) Endotoxin- is a LPS, component of Gm- bacterial cell wall. It is both beneficial & harmful. BeneficialActivate protective immunity.  Induction of cytokine & chemokine  expression of co-stimulatory molecules enhance T cell activation. Harmful- High level of LPS induction of excessive level of cytokines TNF, IL-1,IL-12Septic shock, DIC, ARDS.
  • 53. • B) Exotoxin- secreted from bacteria & causes celluar injury. 1)Enzymes- bacteria secret protease, coagulase, hyaluronidase, fibrinolysin Ex• Stap. aureus produce protease degrade protein that hold keratin together detachment of epidermis from deeper skin.
  • 54. 2)Toxin that alter intercellular signaling & regulating pathway— • Most of the toxins have A sub unit- enzymatic activity B sub unit- binds with the receptor on cell surface & delivers the A subunit into cell cytoplasm. Ex- Bacillus anthracis, V. cholerae.
  • 55. 3) Neurotoxin• Clostridium botulinum, Clostridium tetani • release of neurotransmitters paralysis respiratory failure death. • 4) Super Ag• Stimulate T lymphocyte massive Tcell proliferation & release of cytokines high level of cytokines Capillary leakage & shock.
  • 56. Injurious effects of host immunity 1) Immune response to microbes sometimes causes tissue injury. • a) MTB- causes granulomatous inflammation--delayed hypersensitivity prevents the spread of bacilli but also causes tissue damage & fibrosis. • b) HBV,HCV- causes liver damage due to immune response to infected hepatocyte, not to cytopathic effect .
  • 57. . 2)Humoral immune response to microbes has also pathological consequence • S. pyogenes- Ab produce against streptococcal M protein cross react with cardiac protein damage heart valve RHD. • S. pyogenes- anti streptococcal Ab cross react with glomerular basement membrane  form Ag-Ab complexes deposit in renal glomeruli Post streptococcal GN.
  • 58. • 3)Infection may be associated with chronic inflammatory disorder as well as cancer. Ex• HBV/HCV Hepatitis HCC • H.Pylori Gastritis gastric adenocarcinoma • Schistosomia Chronic cystitis bladder carcinoma.
  • 59. Immune evasion by microbes Micro organism develops many M/A to evade host immune system. 1) Growth in niches that are inaccessible to host immune response a) Microbes are multiply in the lumen of the intestine (C. difficili) / gall bladder (S. typhi) b) Some organism are rapidly invade host cell before humoral immune response become effective. Ex• • Malarial parasite--sporozoite enters into hepatocyte. Trichinella/T. cruzei-enters into skeletal/cardiac muscle.
  • 60. c) Some Parasite form cyst in host cell. Ex- Tapeworm d) During viral latency, viral genes are not expressed. Ex- Herpes virus
  • 61. 2)Antigenic variationVirus can escape immune attack by changing their Ag. Mechanism • High mutation rate • Genetic ressortment • Genetic rearrangement • • • • • • • • HIV Influenza virus Influenza virus Rota virus N. gonorrhoeae Borrelia Trypanosoma Plasmodium
  • 62. 3) Resistance to innate immune response • Resistance to antimicrobial peptide (defensin, cathelicidins& thrombocidin)prevents killing of microbes by neutrophil & macrophage. • Carbohydrate capsule -present on the surface of the micro organism prevent phagocytosis by neutrophil. • Ex- Pneumococci, meningococci, H.influenza
  • 63. • Bacteria by covering with host protein -evade immune defense. Ex- Staphylococcus aureus covered by protein A that bind with Fc portion of Ab phagocytosis. • Some bacteria secret protease degrade Ab. Ex- Niesseria, Haemophilus, Streptococcus • Some organisms replicate within phagocytic cell. Ex- MTB, Liesteria, Leishmania, Trypanosoma, Toxoplasma, Cryptococcus neoformans.
  • 64. • Virus can produce molecules that innate immunity. Ex- Herpes virus, Pox virus produce protein block complement activation. • Some virus produce homologous of IFNα ΙFΝβ /IFN R which the action of IFN. 4) Recognition of infected cell by CD4 TH cell/ CD8 cytotoxic T cell. Ex- HSV,CMV,EBV bind/ alter the localization of MHC-1 impair the peptide presentation to CD8 T cell.
  • 65. Infection in immunosuppressed hosts • Inherited• 1)Patient with Ab deficiencyEx- X-linked aγglobulinaemia• • • • Severe bacterial infectionStrep . pneumoniae Haemophilus influenzae Stap. Aureus • 2)T cell defect- susceptible to infection with intracellular pathogens, virus, some parasite.
  • 66. • 3) Complement deficiency• Strep . pneumoniae • Haemophilus influenzae • Neisseria menigitidis • 4) Defect in neutrophilic function• Stap. Aureus • Gm- bacteria • Fungi
  • 67. Acquired• 1) AIDS • 2) Impaired production of leukocyte leukemia fills the bone marrow with cancerous cell & vulnerable to infection. • 3)Iartogenic cause of immunosuppression• Ex-Immunosuppressive drug. • Disease of organ systems other than immune system• Cystic fibrosis---- RTI with P. aeruginosa • S. aureus • Sickle cell disease----Strep. pneumoniae • Burn---- P. aeruginosa.
  • 68. Spectum of inflammatory responses to infection • 5 major histological patterns of tissue reaction in infections are1) Suppurative inflammation2)Mononuclear & granulomatous inflammation 3)Cytopathic- cytoproliferative reaction4)Tissue necrosis5) Chronic inflammation & scarring-
  • 69. 1) Suppurative inflammationCharacterized by production of large amount pus/purulent exudates consisting of neutrophil, liquefactive necrosis & edema fluid. • Sometimes the lesion are destructive. Ex- Pneumococci spare alveolar wall lobar pneumonia. Staphylococci & Klebsiella destroy alveolar wall form abscess fibrosis.
  • 70. Suppurative inflammation
  • 71. 2)Mononuclear & granulomatous inflammation Granulomatous inflammation- is a distinctive pattern of chronic inflammation characterized by accumulation of activated macrophagesepithelioid cells which may fuse to form giant cells. In some cases there is a central area of caseous necrosis. • Ex- TB
  • 72. Mononuclear cell predominate• Plasma cell abundant Primary & secondary syphilis. • Lymphocyte predominate HBV infection/viral infection of brain.
  • 73. 3) Cytopathic- cytoproliferative reactionIt is characterized by cell necrosis/cellular proliferation, usually with scattered inflammatory cell. a) Some virus replicate within cytoplasm/nucleus & visible as inclusion body. • Ex-Herpes virus, Adeno virus.
  • 74. b) Some virus induce cell to fuse & form multinucleated giant cell. • Ex- Warthin- Finkeldy cells in measles. Herpes virus. c) Some virus causes epithelial cell to detach & form blister • Ex- Herpes virus. d) Some virus causes epithelial cell to proliferate & form wart. • Ex- HPV, Pox virus. e) Finally they contribute to develop malignant neoplasm.
  • 75. 4)Tissue necrosisEx- • Clostridium perfringes- secret toxin gangrenous necrosis. • E. histolytica- liquefactive necrosis. • Herpes virus (brain)/ HBV (Temporal lobe)-severe necrosis. • 5) Chronic inflammation & scarringEx- • Chronic HBV cirrhosis • Schistosoma egg Pipe-stem fibrosis of liver • TB Constrictive fibrous pericarditis.

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