1 Microbes and diseases: what to study-1 1. Causative microbe: name, morphology (shape, size, Gram stain, etc.), physiology (aerobe, anaerobe, etc) and some info on classification (what's it related to?) 2. Pathogenesis and clinical disease: what disease does it cause (signs and symptoms) and how does it do it (capsule, toxins..)? 3. Transmission and epidemiology: how do you get the disease?

2 Microbes and diseases: what to study-2 4. Diagnosis: How does the lab usually identify the causative agent? 5. Treatment: antibiotics prescribed (or not- no cell wall, no penicillin) or other treatment (oral rehydration therapy for cholera). 6. Prevention and control (stop the spread; condoms, kill urban rats..)

Significant diseases of past Scarlet fever Diphtheria Leprosy Plague Typhus Smallpox Polio 3

4 Streptococci: G+ cocci Genera: Streptococcus and Enterococcus Aerotolerant anaerobes, catalase negative –Grow in chains, pairs –Strep: Lancefield groups, viridans, S. pneumoniae Group A strep: S. pyogenes –Pharyngitis, scarlet fever, pyoderma, erysipelas, TSS, necrotizing fasciitis –Sequelae: rheumatic fever and glomerulonephritis Group B strep: S. agalactiae –Infects newborns during birth, major neonatal dis.

5 Characteristics of Streptococcal infections

6 Virulence factors, etc. S. pyogenes (“pus-producing”) –M protein and capsule: avoids phagocytosis –Streptokinase, streptolysins for escape & attack –Pyrogenic erythrotoxins (SPEs) at least 3 different types Cause scarlet fever: fever, rash; toxic shock –Beta hemolytic on blood agar

7 Corynebacterium: G+ rod Found on humans, animals, plants –Normal microbiota, opportunists,& pathogens C. diphtheriae: cause of disease diphtheria –Colonizes the throat, inflammation, fever, and pseudomembrane, release of toxin Pseudomembrane can block throat –Toxin inhibits protein synthesis, kills cells locally Toxin diffuses, kills heart and nerve cells –Antitoxin, antibiotic treatment –Vaccination (DPT); humans are only host.

8 Mycobacterium: G+ rods Many non-pathogenic species, most disease: M. tuberculosis and M. leprae –M. avium-intracellulare: environmental source of lung disease (like TB) in AIDS patients –Mycolic acids as part of complex cell wall Protects against desiccation Protects against destruction by phagocytes Requires acid-fast staining –Generally grow very slowly (chronic illnesses) –Can grow intracellularly

9 Acid Fast stain of Mycobacteria

10 M. leprae Cause of Hansen’s disease, aka leprosy Slow growing, likes it cool; armadillos as model Grows in peripheral nerve and skin cells –Numbness is characteristic of disease Tuberculoid vs. lepromatous leprosy –Mild, severe, respectively, depending on cell mediated immune response. –Numbness vs tissue destruction Spread mostly by direct contact Treatable with antibiotics, but long term

11 Gram negative rods and cocci Endotoxin: Lipid A, the superantigen –Part of LPS of the Gram negative outer membrane –Causes an over-stimulation of macrophages with production of various cytokines –Fever, vasodilation, inflammation, shock, and disseminated intravascular coagulation While Gram negative pathogens can have other virulence factors (capsules, fimbriae, exotoxins), all have endotoxin and are thus dangerous.

12 Truly pathogenic enterics-3 Yersinia: Y pestis is cause of plague, other species cause food-borne infections Plague: 3 cycles: sylvan, urban, and human –endemic in sylvan cycle; mixing of woodland and urban rodents brings urban cycle, fleas jump from dying rats to humans. –Infection leads to large swollen lymph nodes: buboes Bubonic plague, with high fever. Septicemic plague: with DIC, bruising (black death) –Raises mortality from75% to near 100% Pneumonic: coughed out and spread human to human –100% mortality

13 The S.F. earthquake and plague

14 Rickettsiae Gram negative, very small, obligate parasites –Leaky membranes? Most diseases spread by vectors Rickettsiae infect endothelial cells lining blood vessels, avoid digestion in lysozome –Have LPS, generate fever –Damage to capillaries produces spots, rashes –Damage to vessels deprives organs of oxygen

15 Rickettsial diseases R. rickettsii: Rocky mountain spotted fever –Spread by tick bite; rodents are the reservoir –Most common through southeast, mid-south R. prowazekii: epidemic typhus –Humans primary host; vector is the louse –Disease spread in crowded, unhygienic conditions R. typhi: murine/endemic typhus – present in rodent population, vector is the flea

16 Gallery of Rickettsial vectors Rickettsia rickettsiae: tick R. prowazekii: human louse R. typhi: flea

Smallpox Variola major and minor, large DNA virus –Mortality rate 20-60% for major, also blindness –Systemic infection, produced rash In 20 th Century, WHO conquered disease –No animal reservoirs, only human –Effective vaccine –Recognizable signs and symptoms –US vaccination discontinued in 1972 –Declared gone in world in

Smallpox visuals 18

Polio Picornavirus –Small RNA virus –Enterovirus: spread by fecal-oral route Attacks GI tract In small percentage, attacks motor neurons –Leads to paralysis of different muscles, sometimes diaphragm Children in iron lungs to help them breath Lack of muscle function produces skeletal defects 19

Polio continued Epidemics peaked in mid 20 th century –Salk and Sabin raced to produce vaccines –Hailed as heroes On WHO’s list to eliminate 20