INFECTIOUS DISEASES Still an important cause of death among elderly & immunocompromised patients
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, cholerae, Cryptosporidium parvum) parvum) Category C Diseases/Agents Emerging infectious disease threats such as Nipah virus and Hantavirus
BIOTERRORISM AGENTS Category A Highest risk Readily disseminated Highly mortality Eg: anthrax, botulism, s mallpox. plaque
TABLE 8-1 -- Classes of Human Pathogens and Their Lifestyles Taxonomic
Site of Propagation
Prions
Intracellular
Viruses
Obligate intracellular Obligate intracellular Extracellular
Category C Can be engineered for mass dissemination Potential high morbidity & high mortality Emerging infectious disease threats Eg: nipah virus, hantavirus
Bacteria
Fungi
Facultative intracellular Extracellular
Protozoa
Facultative intracellular Extracellular
Helminths
Facultative intracellular Obligate intracellular Extracellular
TABLE 8-4 -- Potential Agents of Bioterrorism Category A Diseases/Agents Anthrax (Bacillus anthracis) Botulism (Clostridium botulinum toxin) 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.) (Brucella sp.) Epsilon toxin of Clostridium perfringens Food safety threats (e.g., Salmonella sp., Salmonella sp., Escherichia coli O157:H7, O157:H7, Shigella) Shigella) Glanders (Burkholderia mallei) Melioidosis (Burkholderia pseudomallei) Psittacosis (Chlamydia psittaci) Q fever (Coxiella burnetti) Ricin toxin from Ricinus communis (castor communis (castor beans) Staphylococcal enterotoxin B
Intracellular
Disease/ causative agents CreutzfeldJacob disease Poliomyelitis
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 Chlamydiae o Ricketssiae o Mycoplasma o Fungus Protozoa
VIRUSES Obligate intracellular parasite 20-300 nm Nucleic acid genome surrounded by CAPSID Classified according to: Nucleic acid genome o Shape & capsid o (+)/(-) of lipid envelope o Mode of replication o Tropism o Type of pathology o (+) inclusion bodies CMV o Herpesvirus o Smallpox & Rabies o Transient, latent infection, tumor production
Synthesize their own DNA, RNA, & proteins but depend on hosts for favorable growth conditions
Obligate Intracellular Bacteria Chlamydia Rickettsia Cannot synthesize Cannot synthesize ATP Replicate inside membrane-bound vacuoles in epithelial cells
C.trachomatis – most common cause of female sterility & blindness
BACTERIA Prokaryotes – have cell membrane but lack membrane-bound nuclei & organelles Cell wall with peptidoglycan Thick (gram positive) o Thin (gram negative) o Classified according to Gram staining o Shape o Need for oxygen o Some with flagella or pilli Colonize body parts of normal people
Depend on Depend on host cell for ATP Replicate inside membrane-bound vacuoles in endothelial cells hemorrhagic vasculitis Transmitted by arthropod vectors
Causes: -Q fever -RMSF
Chlamydia
PRION With prion protein (PrP) Normally found in neurons (+) disease in conformational changes protease resistance Spongiform encephalitis Kuru (human cannibalism) o Creutzfeld Jacob Disease o (corneal transplant) Bovine Spongiform o Encephalopathy (mad cow disease) Variant CJD o
Category B Moderately easy to disseminate Moderately morbidity Low mortality Foodborne or waterborne Eg: brucelliosis, epsilon toxin, glandera, etc.
Helminths Ectoparasites
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 Hyphae @ room temp o Yeast @ body temp o (+) 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
ADAPTIVE – mediated by T & B lymphos
o
o
Blood & blood products (drug abusers, needle sticks) Animals to humans
TRANSMISSION & DISSEMINATION OF MICROBES
1. 2. 3. 4. 5. 6.
HELMINTHS Highly differentiated Multicellular Complex life cycle Sexual – definitive host o Asexual – intermediate o host/vector Disease is due to reaction to eggs or larvae Disease is proportionate to number of organism
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
4. Sexually transmitted 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
SPECIAL TECHNIQUES FOR DIAGNOSING INFECTIOUS AGENTS
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) Chickenpox & Measles o
3. Release of microbes from the body
TRANSMISSION & DISSEMINATION OF MICROBES
Need to infect before transmission Factors: infecting organism & host, virulaent factor Host barriers: Prevent microbe’s entry o Innate or adaptive o INNATE – physical barriers, phagocytic cells, NK cells, plasma proteins
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 Skin penetration (hook worm) o
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 Schistosoma – can enter intact o the skin
HOST DEFENSES AGAINST INFECTION: GIT Acidic gastric Secretions Mucus layer Pancreatic enzymes Bile Defensins Normal flora IgA Host defenses weakened by: Low gastric acidity o Antibiotics o Disturbance in peristalsis o Obstruction o Enterotoxins, exotoxins invasion & mucosal damage, systemic infection
HOST DEFENSES AGAINST INFECTION: RESPIRATORY TRACT Mucociliary defense Alveolar macrophages Damage to mucocilliary defense by: Smoking o Cystic fibrosis o Aspiration o Intubation o
BACTERIAL VIRULENCE Virulence genes in pathogenicity islands *encode proteins for their o 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 Ex: Pseudomonas aeruginosa o
*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 *Female – more prone to o 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: Host cell receptor – for the o virus Cellular transcription Fs o Anatomic barriers (ex.polio) o Local temp.,pH & host o defenses
BACTERIAL ADHERENCE ADHESINS – adhere to host cells or ECM fibrillae (eg. S. pyogenes) S. pyogenes adheres to host o tissues by protein F and teichoic acid projecting from the bacterial cell wall PILI/ FIMBRIAE are filamentous proteins on the surface of bacteria Eg. E. coli, N. gonorrhoeae o
MECHANISMS OF BACTERIAL INJURY Bacterial virulence Bacterial adherence to host cells Virulence of intracellular bacteria Bacterial toxins Injurious effect of host immunity
VIRULENCE OF INTRACELLULAR BACTERIA Infect epithelial cell, macrophage, or both Escape immune response or facilitate spread Gain entry thru immune response Eg.coating with Abs or C3b o (opsonization) phagocytosis When inside the cell – inhibit host protein synthesis, replicate rapidly, & lyse host cell *phagolysosome – kills most o bacteria MTB – prevent fusion of o phagosome &lysosome
BACTERIAL TOXINS EDOTOXINS – component of bacterial cell Eg.LPS (in gm (-) bacteria o Induce cytokines & chemokines o Plays a role in Septic shock, o DIC, ARDS – d/t excessive cytokines EXOTOXINS – secreted by bacterium Enzyme (proteases, o hyaluronidases, coagulases, fibrinolysins) Toxins that alter INTRAcellular o signals or regular pathways (AB toxins) Neurotoxins o (C.botilinum/tetani) - paralysis Superantigens – stimulate very o 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 Can develop infection – o S.pyogenes *Chronic inflammation – provides fertile ground for the development of cancer
*after viral infection = decrease immune response
INFECTIONS IN IMMUNOSUPPRESSED HOSTS
Microorganisms have developed many means to resist and evade the immune system. Mechanisms:
(1) Growth in niches that remains inaccessible/ hidden to host immune response. Eg.intestinal lumen, gallbladder (2) Variation or shedding antigens
Inherited or acquired defects in immunity partial susceptible to specific types of infection X-linked agammaglobulinemia – severe bacterial infections S.pneumoniae o H.influenzae o S.aureus o T-cell defects – intracellular pathogens Complement protein deficiency – susceptible to S.pneumonia o H.influenzae o N.meningitides o AIDS (destroys CD4 T-helper cells), leukemia – opportunistic infections Pneumocystis jirovecii – o common opportunistic
5 PATTERNS of INFLAMMATORY RESPONSE Suppurative inflammation – pyogenic bacteria d/t digestion of normal o structures Mononuclear & Granulomatous inflammation – caused by: Virus, intracellular bacteria, or o intracellular parasites *EXCEPT acute viral infection – o by macrophage Cytopathic-Cytoproliferative inflammation Usually, by a virus o Tissue necrosis – without or few inflammatory cells but NO inflammation C.perfringes, E.histolytica o Chronic inflammation & Scarring – by HBV (cirrhosis)
IMMUNE EVASION BY MICROBES
(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
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
2. Mumps
1. Measles (Rubeola)
Single standed RNA Paramyxovirus family Only 1 strain Cell surface receptors: CD46 – all nucleated cells o Signaling lymphocytic o activation molecule (SLAM) – cells of immune systems a molecule involved in T-cell activation MOT: respiratory droplets
Characteristics/ Morphology: WARTHIN-FINKELDEY CELLS Multinucleated giant cells o w/eosinophilic nuclear & cytoplasmic inclusion bodies Seen in lymphoid organs with o follicular hyperplasia REDDISH BROWN RASH Dilated vessels, edema, o mononuclear perivascular infiltrates KOPLIK SPOT (pathognomonic) Mucosal ulcerated lesions o Marked by: Necrosis, o neutrophils, neovascularization th Appear during 4 day of fever; o nd usually in 2 molar
Morphology Salivary gland pain & swelling 70% bilateral o Mononuclear cells compress o acini PMN & debris – lumen o (parotitis) Aseptic meningitis 0 most common extrasalivary complication (10%) Mumps orchitis – scar & atrophy – causing sterility Pancreatic parenchyman & fat necrosis, pmn-rich Mumps encephalitis – monos
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
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 Meningitis o Encephalitis o Meningoencephalitis o
5. Viral Hemorrhagic Fever
3. Polivirus
CHRONIC LATENT INFECTIONS
4. West Nile Virus
Complications of measles Croup, pneumonia Diarrhea Keratitis (blindness), encephalitis (Subacute sclerosing panencephalitis) Hemorrhagic measles (“black measles”)
Paramyxovirus 2 types of surface glycoproteins Hemagglutinin (w/c enter the o cell) & neuramidase (w/c exit the cell) activities Cell fusion & cytolytic activities o 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
Enveloped RNAs of arena virus: Filoviruses o Bunyaviruses o Flaviviruses o 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: d/t thrombocytopenia or o severe platelet (as low as 500) or endothelial dysfunction increased vascular permeability Activates innate immune response *there are 4 serotypes of dengue
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 HSV-1 – associated with CORNEAL blindness, FATAL sporadic encephalopathy Neonates & immunocompromissed, disseminated HSV infection Large, pink to purple intranuclear inclusions (Cowdry tupe A) Also with halo o
Manifestations Fever, blisters, cold sores (bilateral) Gingivostomatitis (HSV-1) Genital herpes (HSV 2>1) 2 types of corneal lesions: Epithelial keratitis - viruso induced cytolysis of the superficial epithelium stromal keratitis - is o 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 NOT a typical manifestation o 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 Centrifugal = trunk to o extremities
Chickenpox .2wks after respiratory infection .Rash (macule in torso to head & extremities) .Vesicles rupture, crusts, heal
Shingles .Chickenpox Latent REACTIVATION *Dorsal root ganglia
Iatrogenic/ blood transfusion – any age Respiratory secretions & fecal-oral Intranuclear & cytoplasmic o basophilic inclusions Seropositive for life – already o with antibody
High Risks Solid organ transplant patients allogenic BM transplant patients AIDS patient (most common opportunistic organism)
Mode of transmission Transplacental (congenital) Thru vaginal/ cervical secretions (neonatal) or milk (perinatal) Thru saliva – preschool Venereal – after 15 years – ONLY in U.S.
1. Epstein-Barr Virus
Causes infectious mononucleosis (IM) Associated with lymphomas (Burkitt) & nasopharyngeal carcinomas IM occurs in late adolescents & young adults Close contact (*saliva) “kissing virus”
CHRONIC PRODUCTIVE INFECTION 1. Hepatitis B Virus
Diagnosis: Morphology Culture Antibody Antigens PCR (DNA)
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)
1. Staphylococcus
TRANSFORMING INFECTIONS
GRAM POSITIVE BACTERIAL DISEASES 1. Staphycoccal infections 2. Streptococcal & Enterococcal infections 3. Diptheria 4. Listeriosis 5. Anthrax 6. Nocardia
3. Cytomegalovirus
Manifestations of CMV : disseminated Pneumonitis, Colitis, R etinitis
SHINGLES Vesicular lesions, intense itching, burning or sharp pain (radiculoneuritis) Facial paralysis (geniculate nucleus) RAMSAY HUNT SYND o Other VZV associated diseases: Intestinal Pneumonia o Encephalitis o Tranverse Myelitis o Necrotizing Visceral lesions o
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
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 Infected hepatocytes o destroyed by CTL Replicating virus is eliminated o Infection is cleared o 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
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
Gram (+) cocci Grapelike clusters Skin lesions, TSS, respiratory infections, heart lesions, osteomyelitis, food poisoning S. epidermis, S. saprophyticus, S. aureus Toxins Hemolytic toxins o Exfoliative toxins (bullous o impetigo) Superantigens (TSS & food o 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
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. Streptococcus
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)
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: Cutaneous o Inhalational o Gastrointestinal o
CUTANEOUS Anthrax 95% Painless pruritic papule vesicle (2days) rupture black eschar Bacteremia, rare
INHALATIONAL Anthrax Inhaled growth in LN spore germinates toxin release hemorrhagic
o
Activates macrophages
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
Pathogenesis Use antigenic variation to escape immune response: Pili proteins are altered by o genetic recombination Has three or four genes for o 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)
Gm (-) diplococcic Coffee bean shaped Grow best in enriched media (lysed i n 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
2. Whooping cough
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
N.gonorrhea Causes of STD: 1st – C.trachomatis o 2nd – N.gonorrhea o Urethritis in men Asymptomatic in women PID sterility or ectopic pregnancy
Bordatella pertussis Gm (-) coccobacillus Acute, highly communicable Paroxysms of violent coughing followed by “whoop” Vaccine available but high rate due t o antigenic divergence & waning immunity Dx: PCR, culture (less sensitive) Pathogenesis: Colonizes brush border of o 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 Bronchial mucosal erosions o
Hyperemia Copious mucopurulent exudate Peripheral lymphocytosis (90%) Hypercellularity & enlargement o of mucosal lymph follicales & peribronchial LN o o
3. Pseudomonas infection
1. Neisserial infections
Disseminated infection in those lacking complement proteins (MAC) septic arthritis + hemorrhagic papules & pustules Neonatal gonorrhea blindness (conjunctivitis), rarely, sepsis Tx: silver nitrate or antibiotics o
P.aeruginosa Common cause of hospital o acquired Opportunistic, aerobic, gm (-) bacillus a frequent, deadly pathogen of o 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
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: Cause fecal-oral transmitted o 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
5. Chancroid (Soft Chancre)
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
MYCOBACTERIA 1. 2.
6. Granuloma Inguinale (Donovanosis)
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
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
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
1.
Tuberculosis
Chancroid Irregular ulcer: neutrophil debris and fibrin o granulation tissue with o necrosis & thrombosed vessels dense lymphoplasmatic o infiltrates Gram or silver stain – coccobacilli
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 (+)
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
2.
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: parenchymal lung lesion o nodal involvement o Ranke complex: radiologically detectable o calcification o 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 organism drain through o lymphatics into ducts or thru the pulmonary artery microscopic/visible (2mm) Systemic military TB liver,BM,spleen,adrenals,menig o es,kidneys,FT,epididymis isolated-organ TB (mostly systemic, EXCEPT this!) TB meningitis, renal o TB,adrenals,osteomylelitis,salpi ngitis,scrofula,GIT TB
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)
Non-specific signs: early dse: malaise, anorexia, wt. loss low grade fever, night sweats hemoptysis, pleuritic pain AFB. culture, PCR
* FIGURE 8-28 The natural history and spectrum of tuberculosis. (at the back)
MYCOBACTERIUM AVIUM – INTRACELLULARE COMPLEX
MAC Uncommon except in AIDS & low levels of CD4 lymphocytes (<60 cell/mm3) widely dessiminated lungs mononuclear system granuloma, lymphocyte, & tissue destruction rare
LEPROSY
Hansen dse M. leprae Aerosols Grow in cool tissues of skin (32-34C) acid fast, obligate intracellular organisms tuberculoid o lepromatous o intermediate o
Tuberculoid Type dry, scaly skin w/o sensation TH1 (IL-2,IFN-y) hyperpigmented margins w/ depressed centers – seen in patients with intact immune sys. granulomatous, no bacilli or very few anesthesia
Lepromatous Type more severe from, anergic type – severe form of leprosy* symmetric skin thickening & nodules defective T H1 response or dominant TH2 response lepra cells w/ numerous acid fast bacilli - *a macrophage leonine facies hypoesthetic or anesthetic
SPIROCHETES 1. 2. 3.
Syphilis (3 stages) 1° stage 3 wks after contact o single,firm,nontender,raise d,red lesion (chancre) numerous spirochetes o heals in 3 – 6 wks o 2° stage 2-10 wks after primary o skin & tissues maculopapular,scaly, or pustular condylomata lata o lymphadenipahty, mild o fever, malaise, weight loss Tertiary stage rare o after a latent period of 5 o yrs CVS, neurosyphilis,benign o tertiary Sy gummas – white gray o rubbery lesions
o o o
gram (-) STD urethritis, lymphogranuloma venereum
Ricketssia o o
gram (-) typhus fever, rocky mountain spotted fever, scrub typhus
SUMMARY OF BACTERIAL INFECTIONS
Congenital Syphilis crosses the placenta during 1° and 2° early (infantile), late (tardive) homework: “take note of the differences”
ANAEROBIC BACTERIA 1. 2.
Abscesses caused by anaerobes Clostridial infections
Abscess
mixed anaerobic and facultative bacteria foul smelling, pus filled
Clostridium Infections
Serologic Tests for Syphilis Serology - mainstay PCR Nontreponemal tests - measure
antibody to cardiolipin, a phospholipid present in both host tissues and T. pallidum
OBLIGATE INTRACELLULAR BACTERIA Chlamydia
Syphilis Relapsing fever Lyme Disease
RPR,VDRL measure Ab to cardiolipin Treponemal tests FTA-Abs, MHATP
Gram (+), anaerobes, spore former C.perfringes – gas gangrene C.tetani – tetanus C.deficilli – pseudomembranous colitis C.botolinium 0 botulism
FUNGAL INFECTIONS 1. 2. 3. 4.
Candidiasis Cryptococcosis Aspergillosis Zygomycosis (Mucormycosis)
1. Candidiasis
superficial infections esophagitis vaginitis cutaneous chronic mucocutaneous invasive
PARASITIC INFECTIONS 2 general categories: 1. Protozoa Malaria, Babesiosis, Leishmaniasis, African typanosomiasis, Chagas dse. 2. Metazoa Strongyloidiasis, Tapeworms, Trichinosis, Schistosomiasis, Filariasis, Onchoceriasis
*read about MALARIA!
2. Cryptococcosis
Life Cycle and Pathogenesis.
Encapsulated yeast Meningoencephalitis Opportunistic infection in AIDS, leukemic lymphoma patients In soil, bird droppings
Plasmodium vivax , P. ovale, and P. malariae cause low levels of parasitemia, mild anemia, and, in rare instances, splenic rupture and nephrotic syndrome. P. falciparum causes high levels of parasitemia, severe anemia, cerebral symptoms, renal failure, pulmonary edema, and death. The life cycles of the Plasmodium species are similar, although P. falciparum differs in ways that contribute to its greater virulence.
3. Aspergillosis
Mold brewer’s lung in healthy people sinusitis, pneumonia,fungermia in immunocompromised individuals neutropenia,corticosteroids aspergilloma, invasive aspergillosis
The infectious stage of malaria, the sporozoite, is found in the salivary glands of female mosquitoes. When the mosquito takes a blood meal, sporozoites are released into the human's blood and within minutes attach to and invade liver cells by binding to the hepatocyte receptor for the serum proteins thrombospondin and properdin[112] ( Fig. 8-49 ). Within liver cells, malaria parasites multiply rapidly, releasing as many as 30,000 merozoites (asexual, haploid forms) when each infected hepatocyte ruptures. P. vivax and P. ovale form latent hypnozoites in hepatocytes, which cause relapses of malaria long after initial infection.
4. Zygomycosis
mucomycosis bread mold fungi no harm to immunocompetent infect immunosuppressed individuals neutropenia, corticosteroid, diabetes, breakdown of cutaneous barriers nonseptate, irreg. wide hyphae rhinocerebral mucormycosis, lung involvement
Plasmodium falciparum, which causes severe malaria, and the three other malaria parasites that infect humans (P. vivax , P. ovale, and P. malariae) are transmitted by female Anopheles mosquitoes that are widely distributed throughout Africa, Asia, and Latin America. Nearly all of the approximately 1500 new cases of malaria each year in the United States occur in travelers or immigrants, although rare cases transmitted by Anopheles mosquitoes or blood transfusion do occur. Worldwide public health efforts to control malaria in the 1950s through 1980s failed, leaving mosquitoes resistant to DDT and malathion and Plasmodium resistant to chloroquine and pyrimethamine.
Malaria, caused by the intracellular parasite Plasmodium, is a worldwide infection that affects 500 million and kills more than 1 million people each year. According to the World Health Organization, 90% of deaths from malaria occur in sub-Saharan Africa, where malaria is the leading cause of death in children younger than 5 years old.
Once released from the liver, Plasmodium merozoites bind by a parasite lectin-like molecule to sialic acid residues on glycophorin molecules on the surface of red cells. Within the red cells the parasites grow in a membrane-bound digestive vacuole,
hydrolyzing hemoglobin through secreted enzymes. The trophozoite is the first stage of the parasite in the red cell and is defined by the presence of a single chromatin mass. The next stage, the schizont , has multiple chromatin masses, each of which develops into a merozoite. On lysis of the red cell, the new merozoites infect additional red cells. Although most malaria parasites within the red cells develop into merozoites, some parasites develop into sexual forms called gametocytes that infect the mosquito when it takes its blood meal. Plasmodium falciparum causes more severe disease than the other Plasmodium species do. Several features of P. falciparum account for its greater pathogenicity: •
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P. falciparum is able to infect red blood cells of any age, leading to high parasite burdens and profound anemia. The other species infect only young or old red cells, which are a smaller fraction of the red cell pool. P. falciparum causes infected red cells to clump together (rosette) and to stick to endothelial cells lining small blood vessels (sequestration), which blocks blood flow. Several proteins, including P. falciparum erythrocyte membrane protein 1 (PfEMP1), form knobs on the surface of red cells ( Fig. 8-49 ).[113] PfEMP1 binds to ligands on endothelial cells, including CD36, thrombospondin, VCAM-1, ICAM-1, and E-selectin. Ischemia due to poor perfusion causes the manifestations of cerebral malaria, which is the main cause of death due to malaria in children. P. falciparum stimulates production of high levels of cytokines, including TNF, IFN-γ, and IL-1. GPI-linked proteins, including merozoite surface antigens, are released from infected red cells and induce cytokine production by host cells by a mechanism that is not yet understood. These cytokines suppress production of red blood cells, increase fever,
stimulate nitric oxide production (leading to tissue damage), and induce expression of endothelial receptors for PfEMP1 (increasing sequestration). Host Resistance to Plasmodium. There are two ge neral mechanisms of host resistance to Plasmodium. First, inherited alterations in red cells make people resistant to Plasmodium. Second, repeated or prolonged exposure to Plasmodium species stimulates an immune response that reduces the severity of the illness caused by malaria. Several common mutations in hemoglobin genes confer resistance to malaria. People who are heterozygous for the sickle cell trait (HbS) become infected with P. falciparum, but they are less likely to die from infection. The HbS trait causes the parasites to grow poorly or die because of the low oxygen concentrations. The geographic distribution of the HbS trait is similar to that of P. falciparum, suggesting evolutionary selection of the HbS trait in people by the parasite. HbC, another common hemoglobin mutation, also protects against severe malaria by reducing parasite proliferation. People can also be resistant to malaria due to the absence of proteins to which the parasites bind. P. vivax enters red cells by binding to the Duffy blood group antigen. Many Africans, including most Gambians, are not susceptible to infection by P. vivax because they do not have the Duffy antigen. Individuals living where Plasmodium is endemic often gain partial immune-mediated resistance to malaria, evidenced by reduced illness despite infection. Antibodies and T lymphocytes specific for Plasmodium reduce disease manifestations, although the parasite has developed strategies to evade the host immune response. P. falciparum uses antigenic variation to escape from antibody responses to PfEMP1. Each haploid P. falciparum genome has about 50 var genes, each encoding a variant of PfEMP1. The mechanism of var regulation is not known, but at least 2% of the parasites switch PfEMP1 genes each generation. CTLs may also be
important in resistance to P. falciparum. Despite enormous efforts, there has been little progress in developing a vaccine for malaria. Morphology. Plasmodium falciparum infection initially causes congestion and enlargement of the spleen, which may eventually exceed 1000 gm in weight. Parasites are present within red cells, which is the basis of the diagnostic test, and there is increased phagocytic activity of the macrophages in the spleen. In chronic malaria infection, the spleen becomes increasingly fibrotic and brittle, with a thick capsule and fibrous trabeculae. The parenchyma is gray or black because of phagocytic cells containing granular, brown-black, faintly birefringent hemozoin pigment. In addition, macrophages with engulfed parasites, red blood cells, and debris are numerous. With progression of malaria, the liver be comes progressively enlarged and pigmented. Kupffer cells are heavily laden with malarial pigment, parasites, and cellular debris, while some pigment is also present in the parenchymal cells. Pigmented phagocytic cells may be found dispersed throughout the bone marrow, lymph nodes, subcutaneous tissues, and lungs. The kidneys are often enlarged and congested with a dusting of pigment in the glomeruli and hemoglobin casts in the tubules. In malignant cerebral malaria caused by P. falciparum, brain vessels are plugged with parasitized red cells ( Fig. 8-50 ). Around the vessels there are ring hemorrhages that are probably related to local hypoxia incident to the vascular stasis and small focal inflammatory reactions (called malarial or Dürck granulomas). With more severe hypoxia, there is degeneration of neurons, focal ischemic softening, and occasionally scant inflammatory infiltrates in the meninges. Nonspecific focal hypoxic lesions in the heart may be induced by the progressive anemia and circulatory stasis in chronically infected people. In some, the myocardium shows focal interstitial infiltrates. Finally, in the nonimmune patient, pulmonary edema or
shock with DIC may cause death, sometimes in the absence of other characteristic lesions.
