72479938 Chapter 8 Infectious Diseases Robbins and Cotran Pathologic Basis of Disease

INFECTIOUS DISEASES  Still an important cause of death among elderly & immunocompromised patients BIOTERRORISM AGENTS Category A  Highest risk  Readily disseminated  Highly mortality  Eg: anthrax, botulism, smallpox. plaque Category B  Moderately easy to disseminate  Moderately morbidity  Low mortality  Foodborne or waterborne  Eg: brucelliosis, epsilon toxin, glandera, etc. Category C  Can be engineered for mass dissemination  Potential high morbidity & high mortality  Emerging infectious disease threats  Eg: nipah virus, hantavirus TABLE 8-4 -- Potential Agents of Bioterrorism Category A Diseases/Agents  Anthrax (Bacillus anthracis)  Botulism (Clostridium botulinum toxin)  Plague (Yersinia pestis)  Smallpox (Variola major virus)  Tularemia (Francisella tularensis)  Viral hemorrhagic fevers (filoviruses [e.g., Ebola, Marburg] and arenaviruses [e.g., Lassa, Machupo]) Category B Diseases/Agents  Brucellosis (Brucella sp.)  Epsilon toxin of Clostridium perfringens  Food safety threats (e.g., Salmonella sp., Escherichia coli O157:H7, Shigella)  Glanders (Burkholderia mallei)  Melioidosis (Burkholderia pseudomallei)  Psittacosis (Chlamydia psittaci)  Q fever (Coxiella burnetti)  Ricin toxin from Ricinus communis (castor beans)  Staphylococcal enterotoxin B

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Typhus fever (Rickettsia prowazekii) Viral encephalitis (alphaviruses [e.g., Venezuelan equine encephalitis, eastern equine encephalitis, western equine encephalitis])  Water safety threats (e.g., Vibrio cholerae, Cryptosporidium parvum) Category C Diseases/Agents  Emerging infectious disease threats such as Nipah virus and Hantavirus

TABLE 8-1 -- Classes of Human Pathogens and Their Lifestyles Taxonomic

Site of Propagation

Prions

Intracellular

Viruses

Obligate intracellular Obligate intracellular Extracellular

Bacteria

Fungi

Facultative intracellular Extracellular

Protozoa

Facultative intracellular Extracellular

Helminths

Facultative intracellular Obligate intracellular Extracellular Intracellular

Disease/ causative agents CreutzfeldJacob disease Poliomyelitis Chlamydia Streptococcus pneumonia Mycobacterium tuberculosis Candida albicans Histoplasma capsulatum Trypanosoma gambiense Trypanosoma cruzi Leishmania donovani Wuchereria bancrofti Trichinella spiralis

CATEGORIES OF INFECTIOUS AGENTS  Prion  Viruses  Bacteria o Chlamydiae o Ricketssiae o Mycoplasma  Fungus  Protozoa

 

Helminths Ectoparasites

PRION  With prion protein (PrP)  Normally found in neurons  (+) disease in conformational changes  protease resistance  Spongiform encephalitis o Kuru (human cannibalism) o Creutzfeld Jacob Disease (corneal transplant) o Bovine Spongiform Encephalopathy (mad cow disease) o Variant CJD VIRUSES  Obligate intracellular parasite  20-300 nm  Nucleic acid genome surrounded by CAPSID  Classified according to: o Nucleic acid genome o Shape & capsid o (+)/(-) of lipid envelope o Mode of replication o Tropism o Type of pathology  (+) inclusion bodies o CMV o Herpesvirus o Smallpox & Rabies  Transient, latent infection, tumor production BACTERIA  Prokaryotes – have cell membrane but lack membrane-bound nuclei & organelles  Cell wall with peptidoglycan o Thick (gram positive) o Thin (gram negative)  Classified according to o Gram staining o Shape o Need for oxygen  Some with flagella or pilli  Colonize body parts of normal people

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Synthesize their own DNA, RNA, & proteins but depend on hosts for favorable growth conditions

Obligate Intracellular Bacteria Chlamydia Rickettsia Cannot synthesize ATP Replicate inside membrane-bound vacuoles in epithelial cells

C.trachomatis – most common cause of female sterility & blindness

Depend on host cell for ATP Replicate inside membrane-bound vacuoles in endothelial cells  hemorrhagic vasculitis Transmitted by arthropod vectors

Causes: -Q fever -RMSF Mycoplasma  Extracellular bacteria; lacks cell wall  Tiniest free living org.like ureaplasma  Person to person  Atypical pneumonia UREAPLASMA  Sexually transmitted  Nongonococcal urethritis

FUNGUS  Eukaryote  Chitin (+) cell wall  Ergosterol – cell membrane  Yeast cells or hyphae  Some dimorphic o Hyphae @ room temp o Yeast @ body temp  (+) sexual spores or asexual spores (conidia)  Superficial (nails, hairs, skin, dermatophytes, tinea)  Subcutaneous (tropical mycosis)  Deep (coccidiodes)  Opportunistic fungi (Candida, Aspergillus, Mucor, Cryptococcus  Pneumocystis jiroveci in AIDS patients PROTOZOA  Single cell eukaryotes  Can replicate intracellularly or extracellularly

o o o o o o o

Trichomonas vaginalis Entamoeba histolytica Giardia lambia Plasmodium Trypanosoma Leishmania Toxoplasma gondii

TABLE 8-3 -- Some Recently Recognized Infectious Agents and Manifestations

  1. 2. 3. 4. 5. 6.

HELMINTHS  Highly differentiated  Multicellular  Complex life cycle o Sexual – definitive host o Asexual – intermediate host/vector  Disease is due to reaction to eggs or larvae  Disease is proportionate to number of organism

ADAPTIVE – mediated by T & B lymphos

o TRANSMISSION & DISSEMINATION OF MICROBES

Routes of entry of microbes Spread & dissemination of microbes Release of microbes from the body Sexually transmitted infections Healthcare-associated infections Host Defenses against infections

1. Routes of entry of microbes     

Inhalation Ingestion Sexual transmission Insect or animal bites Injection

2. Spread & dissemination of microbes

ECTOPARASITE  Insects or arachnids  Direct effect or as vector  Itching & excoriation  Transmitted disease

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 SPECIAL TECHNIQUES FOR DIAGNOSING INFECTIOUS AGENTS

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Initially, spreads LOCALLY (Cholera, dermatophytes) or INVADE & SPREAD thru blood (malaria), LYMPHATICS (staphylococcus), or NERVES (rabies) Placental fetal route (rubella & syhphilis), birth canal (gonococcal), milk (CMV, HBV) Major manifestations at distant sites (airway) o Chickenpox & Measles

3. Release of microbes from the body

TRANSMISSION & DISSEMINATION OF MICROBES    

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Need to infect before transmission Factors: infecting organism & host, virulaent factor Host barriers: o Prevent microbe’s entry o Innate or adaptive INNATE – physical barriers, phagocytic cells, NK cells, plasma proteins

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o

Skin shedding Coughing Sneezing Urine or feces Insect vectors

TRANSMISSION OF MICROBES FROM PERSON TO PERSON  Respiratory – virus & bacteria (*important)  Fecal-Oral – water borne viruses  Sexual – STDs, HBV, HIV, HSV, HPV  Others o Skin penetration (hook worm)

Blood & blood products (drug abusers, needle sticks) Animals to humans

4. Sexually transmitted infections   

Infection w/ one STI increases the risk with another STD Can be spread from pregnant mother to the fetus  severe damage to fetus/child INITIAL SITE: urethra, vagina, cervix, rectum, oral, pharynx

TABLE 8-5 -- Classification of Important Sexually Transmitted Diseases

5. Healthcare-associated infections    

“nosocomial” infections  hospital acquired (usually after 5 days of admission) Transmitted through blood transfusions, organ transplant, invasive procedures Most common, hands of healthcare providers (wash hands after every patient) Hygiene & hand washing greatly reduce transmission of MRSA & VRE

6. Host Defenses against infections HOST DEFENSES AGAINST INFECTION: SKIN  Keratin layer - *good factor  Low pH (5.5)  Fatty acids  Microbes penetrate INTACT skin or thru breaks o Schistosoma – can enter intact the skin HOST DEFENSES AGAINST INFECTION: GIT  Acidic gastric  Secretions  Mucus layer  Pancreatic enzymes  Bile  Defensins  Normal flora  IgA  Host defenses weakened by: o Low gastric acidity o Antibiotics o Disturbance in peristalsis o Obstruction  Enterotoxins, exotoxins invasion & mucosal damage, systemic infection

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BACTERIAL VIRULENCE  Virulence genes in pathogenicity islands o *encode proteins for their ability to adhere, invade, or deliver toxins  PLASMIDS or BACTERIOPHAGES – virulence factors  PLASMIDS or TRANSPOSONS – antibiotic resistance  QUORUM SENSING – expression of virulence Fs related to concentration (more bacteria = increase virulence)  Secretion of autoinducer peptides – toxin production  BIOFILMS – viscous layer of extracellular polysaccharides that adhere to host tissue or devices  adherence, immune evasion, inc.antibiotic resistane o Ex: Pseudomonas aeruginosa

HOST DEFENSES AGAINST INFECTION: RESPIRATORY TRACT  Mucociliary defense  Alveolar macrophages  Damage to mucocilliary defense by: o Smoking o Cystic fibrosis o Aspiration o Intubation *There are some bacteria that avoid phagocytosis (eg.pneumococcus TB) HOST DEFENSES AGAINST INFECTION: GENITOURINARY TRACT  Urination  Low vaginal pH (glycogen lactobacilli)  Anatomy  Obstruction  Antibiotics (vaginal infection) – w/c destroyed by lactic bacilli o *Female – more prone to infection

HOW MICROORGANISMS CAUSE DISEASE Mechanisms of Injury 1. Enter host cells & directly cause disease 2. Release of toxins/ enzymes (during cell lysis) 3. Host cellular response MECHANISMS OF VIRAL INJURY  Directly damage host cells by entering & replicating inside host cells  Direct cytopathic effects, antiviral immune responses, & transformation of infected cells  Has factors for tissue tropism, d/t: o Host cell receptor – for the virus o Cellular transcription Fs o Anatomic barriers (ex.polio) o Local temp.,pH & host defenses

MECHANISMS OF BACTERIAL INJURY  Bacterial virulence  Bacterial adherence to host cells  Virulence of intracellular bacteria  Bacterial toxins  Injurious effect of host immunity

BACTERIAL ADHERENCE  ADHESINS – adhere to host cells or ECM fibrillae (eg. S. pyogenes) o S. pyogenes adheres to host tissues by protein F and teichoic acid projecting from the bacterial cell wall  PILI/ FIMBRIAE are filamentous proteins on the surface of bacteria o Eg. E. coli, N. gonorrhoeae VIRULENCE OF INTRACELLULAR BACTERIA  Infect epithelial cell, macrophage, or both  Escape immune response or facilitate spread  Gain entry thru immune response o Eg.coating with Abs or C3b (opsonization)  phagocytosis  When inside the cell – inhibit host protein synthesis, replicate rapidly, & lyse host cell o *phagolysosome – kills most bacteria o MTB – prevent fusion of phagosome &lysosome

BACTERIAL TOXINS  EDOTOXINS – component of bacterial cell o Eg.LPS (in gm (-) bacteria o Induce cytokines & chemokines o Plays a role in Septic shock, DIC, ARDS – d/t excessive cytokines  EXOTOXINS – secreted by bacterium o Enzyme (proteases, hyaluronidases, coagulases, fibrinolysins) o Toxins that alter INTRAcellular signals or regular pathways (AB toxins) o Neurotoxins (C.botilinum/tetani) - paralysis o Superantigens – stimulate very large amounts of T lymphocytes  cytokines  capillary leak & shock  Superantigens made by S. aureus and S. pyogenes cause toxic shock syndrome (TSS) INJURIOUS EFFECTS OF HOST IMMUNITY  Tuberculosis – type IV hypersensitivity  HBV & HBC – immune reponse  Rheumatic Fever – cross reaction  Post.Strep GN – type III hypersensitivity o Can develop infection – S.pyogenes *Chronic inflammation – provides fertile ground for the development of cancer

IMMUNE EVASION BY MICROBES Microorganisms have developed many means to resist and evade the immune system. Mechanisms:

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

(1) Growth in niches that remains inaccessible/ hidden to host immune response. Eg.intestinal lumen, gallbladder (2) Variation or shedding antigens

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(3) Resistance to innate immune defenses – capsule, host proteins, protease  can destroy host body (4) Impairment of effective T-cell antimicrobial responses by specific or nonspecific immunosuppression

*after viral infection = decrease immune response

INFECTIONS IN IMMUNOSUPPRESSED HOSTS  

 

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Inherited or acquired defects in immunity  partial  susceptible to specific types of infection X-linked agammaglobulinemia – severe bacterial infections o S.pneumoniae o H.influenzae o S.aureus T-cell defects – intracellular pathogens Complement protein deficiency – susceptible to o S.pneumonia o H.influenzae o N.meningitides AIDS (destroys CD4 T-helper cells), leukemia – opportunistic infections o Pneumocystis jirovecii – common opportunistic

5 PATTERNS of INFLAMMATORY RESPONSE  Suppurative inflammation – pyogenic bacteria o d/t digestion of normal structures  Mononuclear & Granulomatous inflammation – caused by: o Virus, intracellular bacteria, or intracellular parasites o *EXCEPT acute viral infection – by macrophage  Cytopathic-Cytoproliferative inflammation o Usually, by a virus  Tissue necrosis – without or few inflammatory cells but NO inflammation o C.perfringes, E.histolytica  Chronic inflammation & Scarring – by HBV (cirrhosis)

VIRAL INFECTIONS Transient infections .Measles .Mumps .Poliovirus .West Nile Virus .Viral H’gic virus Chronic LATENT infections .HSV .VZV .CMV

Transforming infections .EBV .HPV

Chronic PRODUCTIVE infections .Hepa B

TRANSIENT INFECTIONS

1. Measles (Rubeola)    



Single standed RNA Paramyxovirus family Only 1 strain Cell surface receptors: o CD46 – all nucleated cells o Signaling lymphocytic activation molecule (SLAM) – cells of immune systems  a molecule involved in T-cell activation MOT: respiratory droplets

Characteristics/ Morphology:  WARTHIN-FINKELDEY CELLS o Multinucleated giant cells w/eosinophilic nuclear & cytoplasmic inclusion bodies o Seen in lymphoid organs with follicular hyperplasia  REDDISH BROWN RASH o Dilated vessels, edema, mononuclear perivascular infiltrates  KOPLIK SPOT (pathognomonic) o Mucosal ulcerated lesions o Marked by: Necrosis, neutrophils, neovascularization o Appear during 4th day of fever; usually in 2nd molar Complications of measles  Croup, pneumonia  Diarrhea  Keratitis (blindness), encephalitis (Subacute sclerosing panencephalitis)  Hemorrhagic measles (“black measles”)

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2. Mumps

4. West Nile Virus

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Paramyxovirus 2 types of surface glycoproteins o Hemagglutinin (w/c enter the cell) & neuramidase (w/c exit the cell) activities o Cell fusion & cytolytic activities Inhalation of respiratory droplets  regional LN  replicate in lymphocytes  blood  tropisms: salivary glands & other tissues  desquamation of involved cells, edema, & inflammation  swelling (both side of parotid) & pain Other sites: CNS, testis, ovary, pancreas

    

Arthropod-borne virus Flavivirus (includes Dengue & Yellow fever) Mosquitoes to bird to mammals Humans – accidental host Transmitted by blood transfusion, transplanted organs, breast milk, & transplacental route Usually asymptomatic, 20% mild febrile illness DANGEROUS complicationsL o Meningitis o Encephalitis o Meningoencephalitis

Morphology  Salivary gland pain & swelling o 70% bilateral o Mononuclear cells compress acini o PMN & debris – lumen (parotitis)  Aseptic meningitis 0 most common extrasalivary complication (10%)  Mumps orchitis – scar & atrophy – causing sterility  Pancreatic parenchyman & fat necrosis, pmn-rich  Mumps encephalitis – monos

5. Viral Hemorrhagic Fever

3. Polivirus

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Spherical, unencapsulated RNA Enterovirus w/ 3 major stains, all included in vaccine it uses human CD155 to gain entry into cells Fecal-oral route Infects oropharynx  secreted into saliva  swallowed  multiplies in intestinal mucosa & LN  transient viremia & fever  1/100 invades CNS  replicates in SPINAL motor neurons or BRAIN STEM (bulbar)  POLIO

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Enveloped RNAs of arena virus: o Filoviruses o Bunyaviruses o Flaviviruses Depend on animal or insect host for survival and transmission Transmitted on contact with infected hosts or insect vectors, humans NOT the natural reservoir Some can spread from person to person: Lassa, Ebola, Marburg Mild to acute disease to life-threatening disease with sudden hemodynamic deterioration & shock NO cure or vaccines Potential biologic weapons Pathogenesis NOT well-understood Manifestations: o d/t thrombocytopenia or severe platelet (as low as 500) or endothelial dysfunction  increased vascular permeability Activates innate immune response *there are 4 serotypes of dengue

CHRONIC LATENT INFECTIONS 1. Herpes Simplex virus         

Includes: HSV 1 & HSV 2 Differ serologically Genetically similar Acute & laten Replicate – skin & mucus membrane Vesicular lesions Spread thru sensory neurons Latency associated transcripts Repeated reactivations

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HSV-1 – associated with CORNEAL blindness, FATAL sporadic encephalopathy Neonates & immunocompromissed, disseminated HSV infection Large, pink to purple intranuclear inclusions (Cowdry tupe A) o Also with halo

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Manifestations  Fever, blisters, cold sores (bilateral)  Gingivostomatitis (HSV-1)  Genital herpes (HSV 2>1)  2 types of corneal lesions: o Epithelial keratitis - virusinduced cytolysis of the superficial epithelium o stromal keratitis - is characterized by infiltrates of mononuclear cells  KAPOSI varicelliform eruption  eczema herpeticum is characterized by confluent, pustular, or hemorrhagic blisters  esophagitis - superinfection with bacteria or fungi  bronchopneumonia – d/t intubation o NOT a typical manifestation  Herpes hepatitis

2. Varicella Zoster Virus       

Chicken pox & shingles Mild in children Infects mucous membrane, skin, & neurons LATENT infections – sensory ganglia Transmitted thru AEROSOLA Spread hematogenously Spread vesicular lesions o Centrifugal = trunk to extremities

Chickenpox .2wks after respiratory infection .Rash (macule in torso to head & extremities) .Vesicles rupture, crusts, heal

Shingles .Chickenpox Latent  REACTIVATION *Dorsal root ganglia

SHINGLES  Vesicular lesions, intense itching, burning or sharp pain (radiculoneuritis)  Facial paralysis (geniculate nucleus) o RAMSAY HUNT SYND  Other VZV associated diseases: o Intestinal Pneumonia o Encephalitis o Tranverse Myelitis o Necrotizing Visceral lesions

3. Cytomegalovirus      

Beta group herpesvirus Major envelop CHON binds with epidermal growth factor receptor Latent with WBCs Asymptomatic or mononucleosis like infection in healthy people Gigantism of cell & nucleus Inclusion body surrounded by HAL (OWL’s eye)

Mode of transmission  Transplacental (congenital)  Thru vaginal/ cervical secretions (neonatal) or milk (perinatal)  Thru saliva – preschool  Venereal – after 15 years – ONLY in U.S.

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Iatrogenic/ blood transfusion – any age Respiratory secretions & fecal-oral o Intranuclear & cytoplasmic basophilic inclusions o Seropositive for life – already with antibody

High Risks  Solid organ transplant patients allogenic BM transplant patients AIDS patient (most common opportunistic organism)

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Manifestations of CMV: disseminated  Pneumonitis, Colitis, Retinitis Diagnosis:  Morphology  Culture  Antibody  Antigens  PCR (DNA)

1. Hepatitis B Virus      

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Serum hepatitis Hepadnavirus DNA virus Spread: percutaneously, perinatally, sexually Cell injury secondary to reponse to infected liver cells Envade immune defenses by inhibiting INF-B & down regulating viral gene expression o Infected hepatocytes destroyed by CTL o Replicating virus is eliminated o Infection is cleared If the rate of infection of hepatocytes outpaces the ability of CTLs to eliminate infected cells, a chronic infection is established. This may happen in about 5% of adults and up to 90% of children infected perinatally. In this setting the liver develops a chronic hepatitis, with

GRAM POSITIVE BACTERIAL DISEASES 1. Staphycoccal infections 2. Streptococcal & Enterococcal infections 3. Diptheria 4. Listeriosis 5. Anthrax 6. Nocardia

1. Staphylococcus   

TRANSFORMING INFECTIONS 1. Epstein-Barr Virus    

CHRONIC PRODUCTIVE INFECTION

lymphocytic inflammation, apoptotic hepatocytes resulting from CTLmediated killing, and progressive destruction of the liver parenchyma. Long-term viral replication and recurrent immune-mediated liver injury can lead to cirrhosis of the liver and an increased risk for hepatocellular carcinoma. CTL response is dormant, resulting in the establishment of a “carrier” state, without progressive liver dam

Causes infectious mononucleosis (IM) Associated with lymphomas (Burkitt) & nasopharyngeal carcinomas IM occurs in late adolescents & young adults Close contact (*saliva) “kissing virus”

EBV spread  The major alterations involve the blood, lymph nodes, spleen, liver, CNS, and, occasionally, other organs  Viral ingestion  in normal person, it resolves in 4-6 weeks  In immunosuppressed  EBV targeted nasopharynx & oropharynx  causing B-cell neoplasms IM diagnosis depends on:  90% lymphocytosis with atypical lymphocytes in PBS  Positive heteophile antibody reaction  Specific EBV antigens (viral capsid antigen, early antigen, EB nuclear antigen)

2. Human Papilloma virus      

Non-enveloped DNA virus Papovavirus family >100 types Warts, benign tumors, squamous cell CA (cervix) Initially infect basal cells of epithelium Koilocytosis (perinuclear vacuolization)

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Gram (+) cocci Grapelike clusters Skin lesions, TSS, respiratory infections, heart lesions, osteomyelitis, food poisoning S. epidermis, S. saprophyticus, S. aureus Toxins o Hemolytic toxins o Exfoliative toxins (bullous impetigo) o Superantigens (TSS & food poisoning) Pyogenic inflammation

Morphology  Furuncle or boil  Carbuncle  Hidradenitis suppurativa - infection of apocrine glands, most often in the axilla  Paronychia (nailbeds)  Felons (fingertips)  Staphylococcal scalded skin syndrome or ritter disease - infections of the nasopharynx or skin in children

2. Streptococcus      

Facultative or obligate anaerobe Gram (+) cocci in pairs or chains S.pyogenes: pharyngitis, scarlet fever, erysipelas, impetigo, RF, TSS, GN S. agalactiae: neonatal sepsis, meningitis, chorioamnionitis S. Pneumoniae: community acquired pneumoniae S. mutans: dental caries

3. Diphtheria       

Corynebacterium diptheriae Gm (+) rod MOT: person to person, aerosol or skin shedding Tough pharyngeal membrane Toxin mediated damage to tissues Phage encoded A-B toxin blocks CHON synthesis Immunization – protection against lethal effect of toxin

4. Anthrax      

Bacillus antharcis Spore former Gm (+) rod Box-car shaped Spore – potent biological weapon Major anthrax syndromes: o Cutaneous o Inhalational o Gastrointestinal

CUTANEOUS Anthrax  95%  Painless pruritic papule  vesicle (2days)  rupture  black eschar  Bacteremia, rare INHALATIONAL Anthrax  Inhaled  growth in LN  spore germinates  toxin release  hemorrhagic GASTROINTESTINAL Anthrax  Uncommon  Eating undercooked meat  Nausea, abdominal pain, vomiting  Severe bloody diarrhea  Mortality – 50%

5. Listeria       

Gm (+) bacillus Intracellular Motile, facultative Food borne Exudative pattern of inflammation INTERNALIS – leucine rich proteins on surface bind E-cadherins Protection mediated by IFN-y

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o

Activates macrophages

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6. Nocardia         

Aerobic Gram (+) (+) terminal spores “beaded” Branching N. asteroids – respiratory infection N. brasiliensis – skin infection Patients with defective T-cell mediated immunity Suppurative lesion with liquefaction, granulation & fibrosis

Gram Negative Bacterial infections 1. Neisserial infections 2. Whooping cough 3. Pseudomonas infection 4. Plaque 5. Chancroid (Soft chancre) 6. Granuloma Inguinale

1. Neisserial infections    

Gm (-) diplococcic Coffee bean shaped Grow best in enriched media (lysed in sheeps’s blood agar, “chocolate” agar) N.meningitides & N.gonorrhea – clinically significant

N.meningitides  13 serotypes  Bacterial meningitis in 5-19 years old  Colonize oropharynx  invade respiratory epithelium  circulation  capsule reduces opsonization & destruction by complement  Spread by respiratory route  Tx: antibiotics  10% death N.gonorrhea  Causes of STD: o 1st – C.trachomatis o 2nd – N.gonorrhea  Urethritis in men  Asymptomatic in women  PID  sterility or ectopic pregnancy

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Disseminated infection in those lacking complement proteins (MAC)  septic arthritis + hemorrhagic papules & pustules Neonatal gonorrhea  blindness (conjunctivitis), rarely, sepsis o Tx: silver nitrate or antibiotics

Pathogenesis  Use antigenic variation to escape immune response: o Pili proteins are altered by genetic recombination o Has three or four genes for OPA proteins  OPA-ability to change their antigen; They increase binding of Neisseria organisms to epithelial cells and promote entry of bacteria into cells  Has multiple serotypes  disease with new strain  Adhere to pili+CD46) & invade (OPA proteins) non ciliated epithelial cells at site of entry (nasopharynx, urethra, or cervix)

2. Whooping cough       

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Bordatella pertussis Gm (-) coccobacillus Acute, highly communicable Paroxysms of violent coughing followed by “whoop” Vaccine available but high rate due to antigenic divergence & waning immunity Dx: PCR, culture (less sensitive) Pathogenesis: o Colonizes brush border of bronchial epithelium & invades macrophages Bortedella virulence gene (bvg) – regulates transcription of adhesins & toxins Hemaglutinin adhesins binds with CHON on surface of cells EXOTOXINS – paralyze cilia Cause: LARYNGOTRACHEOBRONCHITIS o Bronchial mucosal erosions

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o Hyperemia o Copious mucopurulent exudate Peripheral lymphocytosis (90%) o Hypercellularity & enlargement of mucosal lymph follicales & peribronchial LN

3. Pseudomonas infection  

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P.aeruginosa o Common cause of hospital acquired Opportunistic, aerobic, gm (-) bacillus o a frequent, deadly pathogen of people with cystic fibrosis, severe burns, or neutropenia  d/t sepsis Resistant to antibiotics Hospital acquired infection, corneal keratitis (contact lenses), endocarditis & osteomyelitis (IV abuses), otitis media (swimmers/diabetics)

Virulence factors  PILI & adherence proteins  binds to epithelial cells & lung mucin  ENDOTOXIN – symptoms & signs of gm (-) sepsis  ALGINATE – slimy biofilm, protects bacteria from antibody, complement, phagocytes, antibiotics  EXOTOXIN – inhibits protein synthesis  PHOSPHOLIPASE C – lyze rbc & degrades pulmonary surfactant  ELASTASE – degrades IgG & ECM  Iron containing compounds – toxic to E.C.  causing vasculitis Manifestations  Necrotizing pneumonia – terminal airways in a fleur-de-lis pattern  Gram (-) vasculitis + thrombosis + hemorrhage – highly suggestive  Bronchial obstruction in CF + P.aeruginosa  bronchiectasis & pulmonary fibrosis  Skin burns  Ecthyma gangrenosum  Bacteremia  DIC

4. Plague

5. Chancroid (Soft Chancre)

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Yersinia pestis, gm (-) facultative intracellular bacterium Transmitted from rodents to humans by fleabites or human to humans by aerosols Causes invasive, frequently fatal infection (black death) Y.enterocolitica & Y.pseudotuberculosis: o Cause fecal-oral transmitted ileiteis & mesenteric lymphadenitis Proliferative within lymphoid cells Yop virulon genes  proteins assemble into type 3 secretion system  binds & injects bacterial toxins (Yops) to host cells  kill host phagocytes & block phagocytosis & production of cytokines

Histologic features  Massive proliferation of organism  Appearance of protein rich & polysaccharide rich effusion  Necrosis of tissues & blood vessels with hemorrhage & thrombosis  Neutrophilic infiltrates Manifestations  BUBONIC PLAQUE – fleabite on legs with pustule or ulceration  draining LN enlarges become soft, pulpy & plum-colored (buboes)  may infarct or rupture thru skin  PNEUMONIC PLAQUE – severe, confluent, hemorrhagic & necrotizing bronchopneumonia with fibrinous pleuritis  SEPTICEMIC PLAQUE – LN & REC all throughout the body develop foci of necrosis + neutrophilia  FULMINANT BACTEREMIAS – DIC with hemorrhages & thrombosis

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Chancroid  Irregular ulcer: o neutrophil debris and fibrin o granulation tissue with necrosis & thrombosed vessels o dense lymphoplasmatic infiltrates  Gram or silver stain – coccobacilli

6. Granuloma Inguinale (Donovanosis)    

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Prepared by: EGBII w/ AFB; 09-17-11

Versus Syphilis (Hard chancre) Hemophilus ducreyi, coccobacilli Acute, sexually transmitted, ulcerative infection 4-7 days after inoculation  tender, erythematous papule Males – lesion in penis; females – vagina and periurethral area Erodes  irregular ulcer  enlargement of regional lymph nodes (buboes)  erodes overlying skin  chronic, draining ulcers Must be cultured in special conditions; PCR

Klebsiella granulomatosis (formerly Calymmatobacterium donovani) minute, encapsulated, coccobacillus Sexually transmitted Untreated  entensive scarring asst’d with lymphatic obst’n & lymphadema (elephantiasis) of external genetalia Dx: microscopy of smears or ulcer biopsy Raised papule  ulceration  granulation tissue  disfiguring scars pseudoepitheliomatous hyperplasia neutrophils and monos in ulcer base Donovan bodies (bacteria in macrophage on Giemsa stain/silver stain smears of exudates)

MYCOBACTERIA 1. 2.

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Tuberculosis Mycobacterium aviumintracellulare complex 3. Leprosy Slender, aerobic rods that grow in straight or branching chain Waxy cell wall composed of mycolic acid Acid fast Weakly gram (+)

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Tuberculosis      

M. tuberculosis, M. bovis Infection thru airborne droplets Organism may be dormant for years within macrophages Reactivation occurs with depressed immune status Delayed hypersensitivity to antigen Tuberculin (mantoux) test   

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NOT specific! (+) means there is exposure or immunization received induration that peaks in 48 to 72 hours

Macrophages - 1° cells infected Replicate w/ phagosomes Bacteremia NRAMP1 gene – gen. of anti-microbial oxygen radicals TH1 response in 3 wks makes macrophages bactericidal Other roles of TH1:  INF-y – for competence of macrophages  iNOS – for oxidative destruction formation of granulomas and caseous necrosis

Non-specific signs:  early dse: malaise, anorexia, wt. loss low grade fever, night sweats  hemoptysis, pleuritic pain  AFB. culture, PCR

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1° TB – ghon (parenchyma) occurs in prev. unexposed (usually in children), unsensitized person usually w/ latent dse some progressive pneumonia like,hillar adenopathy, pleural effusion Ghon complex: o parenchymal lung lesion o nodal involvement Ranke complex: o radiologically detectable o calcification 2° TB @ apex seen in prev. sensitized host shortly after primary or reactivation or exogenous reinfection @ apex of upper lobes cavitation is common initial lesion may heal progressive pulmonary TB in elderly & immunocompromised Miliary pulmonary dse o organism drain through lymphatics into ducts or thru the pulmonary artery microscopic/visible (2mm) Systemic military TB o liver,BM,spleen,adrenals,menig es,kidneys,FT,epididymis isolated-organ TB (mostly systemic, EXCEPT this!) o TB meningitis, renal TB,adrenals,osteomylelitis,salpi ngitis,scrofula,GIT TB

* FIGURE 8-28 The natural history and spectrum of tuberculosis. (at the back)

MYCOBACTERIUM AVIUM – INTRACELLULARE COMPLEX  

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MAC Uncommon except in AIDS & low levels of CD4 lymphocytes (