Download 2. Treatment

Ind iv i dua l
M icro bio lo g y
G
+
Cocci
GG-----
Aerobe
Bacilli
and
G
facultative anaerobe
+
staphylococcus
streptococcus
pneumococcus
meningococcus
Gonococcus
-- enteric bacilli
corynebacterium
M.tuberculosis
diphtheria
Spirillar bacteria ----V.cholera
obligate anaerobe
spore-forming anaerobic bacteria
non-spore-forming anaerobic bacteria
Content
1.biological characteristics
2.pathogenicity------pathogenic factor
phathogenesis
3.immunity
4.laboratory diagnosis(bacteriological methods)
5.prevention and treatment
P a t h o g e n i c Co c c i
G+ cocci – Staphylococcus, Streptococcus, Pneumococcus.
G-cocci – Meningococcus, Gonococcus.
Section1.
Purulent
Infection
St a p h y l o c o c c u s
I. Biological characteristics
1. Morphology:
Gram positive cocci, arranged in irregular, grape – like clusters
No special structure
2.Culture
blood agar----- haemolysis
Colony : 1~2 mm, circular, smooth, shiny surface, opaque, various pigments
3. Classification:
1
Major properties of three species of staphylococci
Main property
Staph. aureus
Pigmentation
Coagulase
Hemolysin
SPA
Pathogenicity
Golden yellow
+
+
+
+++
Staph. Epidermidis
White
_
_
_
-/+
Staph saprophyticus
Citrine
_
_
_
_
4. Antigenic structure:
(1) SPA (staphylococcal protein A)
i) cell wall protein
ii) it combines nonspecifically with the Fc-portion of human IgG
iii) antiphagocytosis
iv) coagglutination
5. Resistance:
(1) resistant to dry; heat (80℃,30min); salt(10~15%)
(2) sensitivity to: basic-dyes(crystal violet); antibiotics and sulfonamides (antibiotic resistance)
II. Pathogenicity
1.pathogenic factor
1).Invasiveness
(1)Surface structure: SPA
(2)Enzyme
Coagulase: A enzyme that convers fibrinogen in citrated human or rabbit plasma into fibrin.
(1).Extracellular coagulase ----an extracellular enzyme which activates a coagulase-reacting factor (CRF)
normally present in plasma , causing the plasma to clot by the conversion of fibrinogen to fibrin (in tube).
(2).Bound coagulase----fibrinogen
fibrin ( in slide)
---Roles: to inhibit the phagocytosis of macrocytes and damage of bacteriacide substances in humor
by coating the organisms with fibrin
2)Toxin---exotoxin
(1) . Staphylolysin: impairment of membrane permeadility; cytotoxic effects on phagocytic and tissue
cells Protein
Staphylolysin-: main pathogenic substance
Form hemolysing-ring around the colony
(2) .Leukocidin: Kill PMNs and M
(3). Enterotoxin:Protein; five types: A-E; Heat stable (boiling for 30 min)Cause a food poisoning
characterized by severe vomiting and diarrhea
(4).Toxic shock syndrome toxin-1 (TSST-1):
Induces multisystsm effects; superantigen effects
(5).Epidermolytic toxin: Cause blistering of skin
4. pathogensis
2
1) purulent infection
(1). local infection skin infection: hair folliculitis; boil; carbuncle; impetigo.
(think pus; limited local area)
(2).organ infection: pneumonia meningitis.
(3).Systemic infection: Septicemia; pyemia
2) toxin diseases
(1). Food poisoning (enterotoxin)
(2). TSS (Toxic shock syndrome)
(3). SSSS(staphylococcal scalded skin syndrome):
3) Staphylococcal enteritis:
dysbacteriosis (superinfection)
III. Immunity
IV. Laboratory diagnosis
specimen: *pus
* sputum (low respiratory tract infection)
* blood (septic shock, osteomyelitis, endocarditis)
* food/faeces or vomit (food poisoning)
* mid-stream urine (pyelonephritis or cystisis)
*direct smear :gram stain
*isolation and identification: blood agar
*coagulose test
*Enterotoxin test and animal test
V. Treatment
Section 2.
St r e p t o c o c c u s
I.Biological characteristics
1.Morphology & cultural properties:
(1).G+ cocci, arranged in chains,
no special structure(capsule of hyaluronic acid in the early period).
(2).high nutritive requirement (blood & serum)
blood agar: *tiny colony ( 0.5~0.7 mm)
* hemolyze erythrocytes in vitro in varying degrees
*faculation/obligate anaerobe
2.Classsification:
It is classified based on the hemolyzation phenomenon and antigenic structure.
(1).Hemolytic activity:
(i) -hemolytic streptococcus
*Incomplete hemolysis, green colotation of the medium surrounding the colony.
*Opportunistic pathogens – subacute bacterial endocarditis (SBE).
(ii) -hemolytic streptococcus (or pyogenic streptococcus)
Complete hemolysis, major human pathogens
(iii) -streptococcus
No hemolyzation, no pathogenicity.
3
(2).Antigenic structure:
(i) Polysaccharide antigen (group-specific antigen). 19 groups
Group A streptococci are main human pathogens
(ii) protein antigen (type-specific antigen).
M protein: *presents in cell wall (group A)
*Anti-phagocytosis
*adhere to epithelial cells
*clump platelet and leukocyte
*heat steable; acid steabl (pH 2)
3.Resistance
*heat labile: 60℃,30 min
*antibiotics sencitivity: panicillin G ,etc.
II.phathogenicity
1. Pathogenic substances (invasiveness & exotoxin):
(1).Invasiveness
(i).surface structure
*LTA(lipoteichoic acid): adhere to sensitive cell
(epithelial cell; platelet; RBC; WBC; lymphocyte; mucous membranes)
* M-protein : ◆anti-phagocytotic
◆M-Ag Ab
hypersensitivity(glomerulonephritis)
◆Common antigen---heart muscle cell(rheumatic fever)
(ii).enzyme
*Hyaluronidase (spreading factor):
Splits hyaluronic acids
bacteria spread
* Streptokinase (SK ):
Lyse fibrin, prevent plasma clotting
bacteria spread
* Streptodornase (SD):
Resolve DNA
bacteria spread
(2).Toxins---exotoxin
(i) Streptolysin (hemolysin)
Streptolysin O (SLO)
Streptolysin S(SLS)
oxygen-labile hemolysin
oxygen stable
O2
O2
(-SH
-S-S-)
(-SH
-SH)
antigenicity-----ASO
weak antigen
(antistreptolysin O)
destroy WBC, pletelet
destroy WBC
virulence of MΦ, N.C
virulence of many tissues
protein
polypeptide
MW 60,000
28 amino-acid
(ii) Erythrogenic toxin (or pyrogenic toxin /scarlet fever toxin)
*produced by most strains of group A streptococci
*cause scarlet fever
*possess antigenicity, antitoxin specifically neutralize the toxin
4
* protien heat stable
2. Diseases of streptococcal infection
1). Infections of group A (-hemolytic streptococci)
(1). local purulent infections: *pharyngitis, *erysipelas *puerperal fever
(2). systemic infection : * septicemia *scarlet fever
(3). poststerptococcal diseases (hypersensitive disease)
(i) acute glomerulonephritis ( group A)
mechanism:
*type III hypersensitivity (most)
*type II hypersensitivity
M protein- Ab complex
common Ag
(ii) Rheumatic fever (many types of group A streptococci)
mechanism:
*immune complex  (deposition) heart, joints  type III hypersensitivity
*common Ag  cross –reaction heart type II hypersensitivity
2) Infections of -hemolytic streptococci:
normal flora : throat/nasapharyn
*SBE(subacute bacterial endocarditis)
damaged heart valve
fever, heart murmure;enlarged spleen; anemia.
I V. I m m u n i t y
V. L a b o r a t o r y d i a g n o s i s
1. Isolation & identification of pathogen
2. ASO test: ASO titer > 1: 400 units, help to diagnose rheumatic fever.
VI. Prevention & treatment
*Treat the pharyngitis and tonsillitis in time, avoid the post streptococcal diseases.
*Antibiotics and chemical agents: penicillin G for the first choice
Section 3.
P n e u mo c o c c u s
1. Belong to the Streptococcus ( Streptococcus pneumoniae ),
2. G+, diplococcus, lancet shape,
arranged in pair, capsule of polysaccharide
3. Blood agar, 0.1% glucose, 5~15%CO2
4. small colony, α- haemolysis, smooth colony (virulent strain)
‘draughtsman’colony(incubation over 24 hour)
5. Pathogenic factor: capsule( antiphagocytosis)(S→R); pneumolysin
6. Disease: pneumonia , bacteraemia; meningtis
7. Treatment: sensitive to a wide range of antimicrobia agent. eg.Penicillins*,
Section 4.
Neisseria
Gram negative cocci, usually arranged in pairs. Some are normal inhabitants in respiratory tract. Others
are human pathogens (eg: gonococcus,meningococcus )
Common biological characteristics
1.Gram negative cocci, kidney-shaped, in pairs have capsules and pili
5
2.Need enriched medium (chocolate blood agar )
3. 5~10%CO2
4.Resistance: very weak “fragile”, extremely sensitive to drying, heat, cold…
Neisseria meningitidis
I. biological characteristics
II.Pathogenicity and immunity
1. Pathogenicity:
(1) Human is the only natural host for pathogenic meningococci.
Child: susceptible (lacking specific Abs)
(2) Pathogenic factor:
*Pili– attach to nasopharyngeal mucosa
*capsule – antiphagocytosis
*endotoxin – main pathogenic substance capillary tube, small blood vessel
2.Pathogenesis:
epidemic cerebrospinal meningitis
clinical typing: common, outbreak,septicemic type
3.Immunity:
group-specific antibody, cross-immunity between groups.
III. Laboratory diagnosis
1. specimen: spinal fluid, blood, nasopharyngeal swabs .
(*note: “fragile” bed-side inoculation)
2. direct smear : smear Gram stain (G- diplococci, within white cells)
3. isolation and identification:
specimen serum broth  chocolate blood agar plate (5~10% CO2 ,37C )  Gram stain and biochemical,
serological identification
4. serologic test : to detect the unknown Ag with given Ab
IV. Prevention and treatment
1. Polysaccharide vaccine (group A, C)
2. Penicillin; cefotaxime; chloramphenicol
Neisseria gonorrhoeae
1. Pathogenic factors:
* Pilli: attach to epithelial cells (urinary-gentital, RBC)
* IgA 1-protease: break down surface IgA antibodies.
*Outer membrane protein (OMP):
2. Diseases:
*Gonorrhea (STD: sexually transmitted disease)
acute urethritis(male); pelvic inflammatory(female)
*ophthalmia neonatorum→blindness
3. Laboratory diagnosis:
Specimen: purulent secretion of genitourinary tract
Isolation and identification: direct smear, culture, biochemical tests
4. Prevention and treatment
*penicillin----- Gonorrhea
*silver nitrate---- ophthalmia neonatorum
6
------ Cheng Yizhe
Enteric Bacilli
I. Common properties:
1. Similar shape: G- rods, most possess flagella and pilli. No spores, certain members possessing
capsules.
2. Biochemical reactions are active and diverse.
Many kinds of carbohydrates and proteins can be utilized and form various products.
Differentiation: e.g. Lactose fermenting bacteria – enteric nonpathogens
Non-lactose fermenting bacteria – enteric pathogens
3. antigenic structure is complex
(1) *O antigen - specific polysaccharides of LPS:
Repeating sequence of carbohydrates, different enteric bacilli vary
in the constitution and their arrangement.
Basis of serological classification
*S-R variation: Smooth colony (virulent)  lose O-specific
polysaccharides  rough colony (non-virulent)
(2) Surface Ag:
Polysaccharides that cover the O Ags (e.g. capsule Ag)
Main surface Ags: Vi antigen (S. typhi), K antigen (E. coli)
Inhibit specific agglutination of O antiserum
Associated with invasiveness of enteric bacilli
(3) H Ag – flagella protein:
Specificity of H antigen is determined by the arrangement and stereoscopic form of amino acids
within polypeptides.
Basis of serological classification.
4. Resistance:
(1) Killed by heating at 60C for 30 min.
(2) Some strains resistant to the action of bile salts.
(3) Antibiotics and other chemotherapy agents are effective against members of the family, but the
susceptibility pattern frequently varies in strains.
5. Produce endotoxins and/or exotoxins
6. Final identification depend upon their chemical and serological reaction
Section I.
Escherichia coli
I. Biological characteristics:
1. Shape and structure: G- rods, possess flagella and pilli.
7
2 .Biochemical reactions (extremely active and complex):
(1) Lactose fermentation test: “+”
Differential media : EMB(eosine methylene blue) –metallic green
MacConkey agar plate – red color
(2) IMViC test: + + - 4. Antigenic structure:
O Ag---- more than 164 cross -rection
H Ag ---- more than 60 specific
(flagellar)
K Ag (L, A and B) ---- more than 100
e.g. serotype is expressed as O111:K58 (B4):H2
II. Pathogenicity
1. pathogenic factors
(1) invasiveness:
K Ag; Pili (fimbriae) ;
CFA (colonization factor Ag)
Specifically adheres to the epithelial cell lining the small intestine
(2) endotoxin: cell wall lipopolysaccharide ; fever / shock
(3) O Ag, K Ag: anti-complement; anti-phagocyte
(4) enterotoxin (exotoxin)
protein, under genetic control of a tansmissible plasmid; consists of LT and ST
LT (heat labile enterotoxin)
ST(heat stable enterotoxin)
Heat:
labile 65 ℃,30min
stable 100℃,30 min
MW:
73,000
4,000~5,000
Ag:
Ag→Ab
no
Structure: 1A(A1,A2) and 5B
a and b
Mechanish:
2. Infection
(1). extaintestinal infections ----caused by E. coli
opportunistic pathogens
*urinary tract infection (the most common )
*G- bacteremia ;septicemia
* neonatal meningitis (new born)
(2). diarrheal diseases------caused by certain serotypes of E.coli
① Enterotoxigenic E.coli (ETEC)
LT and/orST ;
Diarrhea; children(under 5 years),adult(travellers)
Nausea, vomiting, abdominal cramps
② Enteropathogenic E.col i(EPEC)
No exterotoxin;
Diarrhea; infantile enteritis severe→death
Less in adults
③ Enteroinvasive E.coli(EIEC)
No exterotoxin; endotoxin
Diarrhea, like dysentery;(several organisim.
Children, adults
Large intestine)
8
④ Enterohemorrhagic E. Coli(EHEC)
or Vero cytotoxin-producing E.coli(VTEC)
endotoxin; hemorrhagic colitis;
III.
Laboratory diagnosis
1. Specimen: feces, blood, pus, ……
2. Isolation and identification: * Biochemical reactions
* serologic identification
IV.
Investigation in public health bacteriology
– indicator of fecal pollution (food/water)
1.Detecting number of coliform bacteria:
Normal number < 3 / 1000 ml sample.
2.Detecting total number of bacteria:
Normal number < 100 colonies / ml (g) sample.
V . Tre a t me n t a n d c o n t ro l
I.
Section 3.
Biological characteristics
Shigella
1. G-, non-motile, possesses pili
2. biochemical reaction
lactose fermentation: (shigella sonnei late fermentation),
3. antigenicity: O Ag (pili Ag), K Ag
4. Classification: 4 groups, 43 serotypes
5. Resistant: Sonnei > flexneri > dysenteriae
6. Variation: (1). antibiotic-resistance (R plasmid);
EMB---non color colony
(2). SR
II. Pathogenesis and Immunity
Human beings – the only natural hosts
1. Pathogenic factor:
Infecting dose: 10~100 organisms
(1).Pili – adhesion ileum intestinum end epithelial cell
(2).Endotoxin – fever, shock; inflammatory; rectal cramp
(3).Exotoxin: S. dysenteriae I, II  shiga toxin
2.Course:
organisms  oral route
suddenincubation 2~3 days/12 hour
abdominal colic

watery diarrhea

fever, malaise

local inflammation ulceration

bloody mucopurulent stool, abdominal cramp, tenesmus
*acute dysentery(bacillary dysentery)
9
diarrhea , 39℃,blood stool more than ten times, vomit
*chronic dysentery : diarrhea
3.Immunity
IgA persistent short, no IgG
III.Laboratory diagnosis
1.Isolation and identification
Stool / rectal swabs  selective media  biochemical, serological, and animal tests
2.Rapid diagnosis
A. Fluorescence-bacterial particle method
B. Co-agglutination
I V. T r e a t m e n t
Section 4.
I. Biological characteristics:
Salmonella
1. Morphology and biochemical reactions:
(1) Morphology: G-, peritrichous, non spore-forming
(2) Culture: grow in simple cultural media, EMB,non-color colony
(3) Biochemical reactions:
--------the basis of classification and identification
2.Antigenic structure and classification
(1). O antigen (somatic antigen)
group specific Ag: 42 groups
(2). H antigen (flagella antigen)
Type specific Ag:
a. Phase 1 – specific phase
b. phase 2 – nonspecific phase
(3). Vi antigen(virulent Ag)
surface polysaccharide; Ag leak;
antiphagocytosis
3.Variation
(1) S→R Variation: lose O-specific polysaccharides
(2) H→O Variation: lose of flagella
(3) V→W Variation: lose of Vi-Ag.
4.Resistance
60℃ 1 hour ; 65℃ 15~20min
living: 2~3 weeks in water , 1~2 month in feces
resistance to certain chemicals, e.g. brilliant green
II. Pathogenesis and immunity
1. Pathogenic factors
(1) Invasiveness
Pili---adhance Vi antigen ---antiphagocytosis
(2) Endotoxin
WBC↓; shock ; activited complement→inflammant
(3) Enterotoxin
S.typhi murium: LT/ST
2. Pathogenesis
10
(1) Septicemia: (S. Choleraesuis)
Pneumonia; osteomyelitis; meningitis(neonates, very young child)
(2) Enterocolitis (Food poisoning)
World wide; incubation period: 8~48 hour
headache, abdominal pain, nausea, vomiting, fever , watery diarrhea
(3) Enteric fever:
Organism  typhoid (caused by S. typhi)
paratyphoid (caused by S. Paratyphi A,B,C)
 infective dose: 106~109 organism; 103or less than 100
Courses of the disease (3 stages):
Organism
 comtaminate water or food via eating
ingestion(some destroy by gastric acid)

adhere in the small intestine by pili

phagocytosis by tntestinal lymphnodes (macrophages)
growing  thoratic duct
Blood stream ----------------------------------------primary bacterimia

Organs and tissues
(liver, kidneys, spleen, bone marrow, gall bladder)
phagocytosis multiplication
Blood stream-------------------------------------Secondary bacterimia
(high fever, enlargment of spleen, slow pulse)

organs : capillaryrose spots
done narrowanemia
kidneyorganism excret out
gall bladderintestinal tructsexcret out

Major intestinal lymphnode necrosis ulcer (Hypersensitivity
IV)

testinal wall necrosis, ulcer

enterobrosis(intestinal perforation)
Recover
dead.
Characteristics of the disease: two times of bacteremia, continuous
fever, liver and spleen enlargement, rose spots, severe complications.
3. Immunity
Enteric fever: *persistant immunity after disease.
*The main anti-infectious immunity is CMI.
*humoral immunity destroy the organism which into the blood
11
Ab titer can continue for a long time after recover
 gastroenteritic: local Ab
septicemia:
monophagocytocis, Ab
III. L a b o r a t o r y d i a g n o s i s
1. Bacteriological methods
(1) *Enteric fever: collect specimen according to the stages of the disease,
1st week----blood; 2nd~3rd week ------ feces or urine.
*Food poisoning: collect feces, food.
*septicemia: blood
(2) Systemic biochemical and serologic identification.
2. Serological methods (Widal test)
(1) To detect the unknown Ab with given Ag(O,H,HA,HB) – tube agglutination.
(2)Normal serum titer: O < 1:80; H < 1:160; H (A/B) < 1:80
IV.
Prevention and treatment
1. Vaccination – Triple vaccine (TAB)
2. Antibiotics: chloramphenicol (oral, 14 days) and other
Bacteremia-----high dose ampicillin, 10~14 days
-------Cheng
yizhe
Vibrio (V. cholera)
V. cholera – cause cholera (an outbreak infectious disease)
– two biotypes: classical biotype
eltor biotype
I. Biological characteristics:
1. Gram negative, short curved rods, single polar flagellum, pili, sexpilis
2. Culture
(facultative)Aerobe, 37℃
halophilic, grow in high pH (8.5 – 9.5) medium,
3. Antigenic structure
O Ag stable heat group specificity(130 serogroup, V. Cholera O-1)
H Ag labile heat non- specificity
4. biochemical reaction
five sugar fermentation test: + - + + +
5. resistant
*live for 1~3 weeks in water
*resistant basic, cold
*sensitive to heat(55℃ 15min,100℃ 1~2min) dry acid(gastric acid 4min) Antibiotics
II. Pathogenicity:
12
1. Pathogenic factor
(1).Invasiveness: flagellum, pili
(2).Cholera enterotoxin (similar to LT) MW: 84,000
*B subunits (five) – 56,000; Ag high; bound unit, attaches to the
receptor (GM1) on the epithelial cells of small intestine.
*A subunits (A1 ,A2) –28,000; Ag weak ;active unit, enters the cell,
stimulates adenylate cyclase  cAMP .
2. Disease-----cholera
Organisms  oral route (contaninated water, food)

stamoch(gastric acid)

attach to the small intestine epithelial cells(non-penetration)

multiplication

cholera toxin

adenylate cyclase

cAMPconcentration 

secreting effect 

devere diarrhea (rice-water stools )
*patient may lose as much as 10 to 15 liters of liquid peir day
*rapid dehydration and hypovolaemic shockdeath in 12-24 hour
*“rice-water stools”---mucus, epithelial cells, large number of vibrios
* recover: gallbladder have some organism
III.Immunity
1. Nonspecific immunity: Gastric acid
2. Specific immunity: Abs (SIgA)
3. Persistent immunity to the same serotype
I V. L a b o r a t o r y d i a g n o s i s
1. Rapid diagnosis
rice-water stools--- directly smear: Hanging-drop observation;
Gram stain
2. Isolation
Basic peptone water, 37℃, 3~6 hours, grow on the surface
3. Identification
Slide agglutination test
fermentation reaction
V. P r e v e n t i o n a n d t r e a t m e n t
1. Vaccine
13
*Inoculation of dead bacteria-vaccine
*Live attenuated oral vaccines(against O1 , O139)
*Genetic engineering vaccine is being studied. (subunit vaccine + toxoid)
2. give the life-saving replacement of fluid and electrolytes
3. Antibiotics: tetracycline; chloramphenicol
-------Cheng
yizhe
A n a e ro b i c b a c t e r i a
Section 1.
I n t ro d u c t i o n
1. Anaerobic bacteria:
Spore-forming anaerobes-----Clostridium(G+ bacilli)
Non-spore-forming anaerobes-----polymorphic
more than 30 genera (G+ and G- cocci, G+ and G- bacilli)
2. Distribution:
Clostridium: endospores, in nature
Non-spore-forming anaerobes: members of normal flora
(1011 bacterium in 1g feces)
3. Infection:
Spore-forming anaerobes
Non-spore-forming anaerobes


Exogenous
Exotoxin
 Typical clinical symptoms
endogenous
endotoxin & other invasive factor
inflammation
similai sympotems
abscess
Septicemia
 Treatment by antitoxin Treatment by antibacterial drug
4.Anaerobic culture
1).biological method-----beef medium
2). Physical method------anaerobic jar
3). Chemical method------chemical reaction(blood agar)
Section 2.
Spore -f orming anaerobic bacteria – C lostridium
I. Clostridium tetani
1. Biological characteristics:
*Peritrichate, endospore – round, terminal spore(“drum-stick”)
*culture: blood agar----completely hemolysin; ‘feather’ colony
*resistance:
several years in soil (spore)
sensitive to penicillin(vegetative form)
14
2. Pathogenesis:
1).condition
*deep ,narrow and mixture with soil
Wound+spore
*necrotic tissue
*pyogenic bacteria mixture infection
(puncture; gun shoot; burn; animal bite)
2).pathogenic substance
* tetanospasmin (neurotoxin)
protein 150,000 ; α toxin subunit, β bound subunit
1μg----lethal
Ag→Ab(tetanus antitoxin TAT)
potent neurotoxin
3).mechanism :
Spores  vegetative bacteria  grow locally
↓
tetanpspasmin (neurotoxin)
↓ blood
anterior horn cells of spinal cord ,binds to ganglioside receptor and blocks
release of inhibitory mediators (eg. glycine)
causes convulsive contraction of voluntary muscle.
4).Clinical manifestation:
*local muscle apasm – lock jaw ; sardonic grin
*progressive spasm – opisthotonus, respiratory failure
3. immunity
humoral immunity-----antitoxin
4. diagnosis
*morphology not value
*clinical picture
5. Prevention and control:
*Active immunization: toxoid DPT (Diphtheria, Pertussis, Tetanus)
*Passive immunization: TAT (tetanus antitoxin), early & enough
* wound---debridement
*antibiotics (penicillin)
II. Clostridium botulinum
1. Biological characteristics:
1). Morphology
* Large rod ;
*endospore: oval, sub-terminal; no capsul; pertrichous
2). Culture
* blood plate-------hemolysis
3).resistant
*living in gastroliquid for 24 hr
15
*spore: 180℃ 5~15min ; 100℃ 3~5h ; 120℃ 5min
2. Pathogenesis:
1).pathogenicity substance-----Botulin
*the most toxic exotoxin
1 mg botulin can kill two million mice.
Lethal dose for human being is about 1 g).
*Eight types of C. botulinum: A, B, C, C, D, E, F, G
A, B, E, F – main pathogens to human being
*Neurotoxin
inducing muscle paralysis in three steps:
binding to receptor on nerve synapse
entrance into nerve cell
blocking release of acetylcholine from the cell
*heat labile 100℃ 10min
*protein
2).disease
*food poisoning (Neurotoxin) ----- fatal
*C.botuliumcontaminated food
↓growing
producing botulin
↓
ingestion
↓
intestinal tract
↓absorb
blood
↓
CNS
↓
inhibitin the release of acetylcholine
↓
paralysis
*clinical manifestation: eye and throat paralysis (early signs) 
respiratory and cardiac failure  death
3. Immunity: no induce antitoxin; no immunity
4. Laboratory diagnosis:
* anaerobic culture of food;
* toxin test----- feces ; vomit
5. Prevention and treatment
*food boiling
* to neutralize unfixed toxin by give polyvalent antitoxin
Section 3. Non-spore-forminga n a e ro b i c b a c t e r i a
16
*70-80% infection of oral, intestinal tract, urogenital tract are caused by non-spore-forming anaerobic
bacteria
I. Biological characteristics:
1. G+ bacilli : polymorphic, no- motile, growing slow,
biochemical react slowly
* Bifidobacterium
* Lactobacillus
2. G- bacilli : capsul, pili, no motile,
*Bacteroides--- B. fragilis;
B. melaninogenicus
*Fusobacterium---F. nucleatum
+
3. G cocci:
*peptococcus
*peptostreptococcus
cause infection with other bacteria
4.G cocci:
*Veillonella
cause infection with other bacteria
II. Pathogenesis:
*Infection mixed with other aerobes
*Anaerobic environment
pathogenic condition
chronic consumptive disease
maligmant tumor
immunity function lower
diabetes
radiotherapy
chemotherapy
barrier destruction
dental extraction
enterobrosis
open fracture
tissue necrosis
local anaerobic environment
ischemia
flora disequlibrium
*Pathogenic factors: LPS, capsule, enzymes
* diseas
nonspecific infection: chronic; purulent local inflammation, abscess, tissue necrosis, septicemia
III. Laboratory diagnosis:
Direct smear; Anaerobic culture
IV. Prevention and control:
*Surgical treatment
*Antibiotics : penicillin metronidazole
17
-------Cheng
yizhe
Mycobacterium
Types of Mycobacterium:
M. tuberculosis
M. Bovis
M. africanus
*Non-tuberculosis mycobacteria
*M. leprae
*M. tuberculosis
Section 1.
M. tu bercul osis
I. Biological characteristics:
1. morphology
*thin , straight or slightly curved rod ,
*G+; acid-fast stain----red
*non-motile; non- sporing; non-capsulate
*thick, complex, lipid-rich-waxy cell wall
2. culture
*obligate aerobes;
*Special nutrient requirement:
whole eggs(yolk), glycerol, asparagine, malachite green, potate
*Slow growth: generation time – 18 h~24h(primary isolation—8 weeks)
Colony: “cauliflower”
Pellicle on surface of liquid media
3.Resistant
*Resistant to drying (especially in sputum, 6-8 months)
*resistant to: acid( 3% HCl, 6% H2SO4)
alkalis( 4% NaOH)
*Sensitive to : moist heat---60℃ 30min,70℃ 3min
disinfectants-- alcohol, glutaraldehyde, formaldehyde
(5%lysoform: no sputum---5min, sputum---1-12h)
drugs---rifampin, para-aminosalicyclic acid,
streptomycin, isoniazid, pyrazinamide
U.V.
4.Variation:
*drug resistance variation
*virulent variation ------BCG (Bacliie Calmette-Guerin)
II. Pathogenicity
1. Pathogenic substance:
(1) Lipid
Possess 40% of the cell dry weight, or 60% of the cell-wall dry weight
Phosphatide
18
Stimulate monocytes proliferation---form tubercle
Inhibit proteinase--- form caseous necrosis
Mycolic acid
A large fatty acid
Associated with acid-fast property
Cord factor Associated with virulence
Inhibit migration of leukocyte to form chronic
granuloma
Bind to mitochondrial membranes, cause
functional damage to respiration and oxidative
phosphorylation
Wax D----Act as an adjuvant
Sulfatides-----Inhibit the fusion of phagosome and lysosome
(2) Protein-----Ag; protein-Wax D→allergic response
(3) Polysaccharide(capsul?)
Connected with Wax D
2. Disease: tuberculosis
Usually a respiratory infection, others as wound, food can cause
infection---lung, intestin, kidney, skin, lymphonode, bone, joint
Pulmonary tuberculosis:
primary tuberculosis
organism→respiratory tract→pulmonary alveolar→lesions
→hilar lymph nodes→swelling→fibrosis→natural cure
 post-primary tuberculosis
organism→infection again→inflammation→necrosis→tubercle
→fibrosis/caseation necrosis
pathogenic mechanism
infiltration ----------PMN, monocyte
tubercles-------monocyte→phagocytose bacteria
lipid
epithelioid cell
fuse
multinuclear giant cell surrounded by lymphocyte
tubercles
fibrosis------a little bacterium, immunity→calcium diposis
caseation necrosis----immunity↓,bacterium multiplication, allergy
→necrotic tissue in a semisolid cheesy state
or necrotic tissue effluvium→cavities
III. immunity
1. The main anti-infectious immunity is CMI
2. Infection immunity
3. CMI and DTH
I V. T u b e r c u l i n t e s t
19
*OT (old tuberculin):
TB  Glycerol broth 4-8 weeks  100C, 1 h  filtration
 concentration (1/10)
*PPD (purified protein derivative):
TB  special media 6-8 weeks  TCA precipitation
1. Principle: DTH
2. Result and interpretation
PPD injection
 24-48h
induration, erthyema
“-”---  < 5mm:  no TB infection
 early stage of primary infection
 miliary tuberculosis or tuberculosis meningitis;
 virus infection; tumor, AIDS;
 use of immunosuppressive agents
“+”--- 5mm   <15mm: hypersensitive to M. tuberculosis ; immunity
“++”---   15mm: active TB perhaps
3. Application
* Basis of BCG inoculation, detect immunity effect
*Diagnosis for young children tuberculosis
*Epidemiological investigation
*cellular immunity test of patients with tumor
V. L a b o r a t o r y d i a g n o s i s
1. Specimen: sputum, urine, CSF, etc.
direct smear----acid-fast stain
2. culture---specimen concentration
sputum 4% NaOH/3% HCl/6% H2SO2 , 30 minkH2PO3, 15-30min
centrifuged deposit inoculate media 8 weeks
3. Animal test---guinea pig
4. Immunity diagnosis----ELISA
5. PCR
VI. Prevention and control
1. Specific prevention: BCG
2. Prophylactic chemotherapy:
isoniazid
-----Cheng
yizhe
ChlamydiaeI. Biological propertiessmall non-motile prokaryotic microbes, filterable
(0.2-0.4um) ,
2. cell wall, G- similar to G- bacillus,
3.contain DNA and RNA ,
20
4.obligate intracellular parasite,
5.unique life-cycle ,
6.classification,
unique life-cycle :Elementary body : very little (0.3μm in diameter), dense , infectious form;Initial body:
larger (1μm in diameter), less dense,
non-infectious, replication form
Elementary body → phagocytic engulfment → replication form →initial body →inclusion body →lots
of elementary body →release from cell, infect another cell, 40hrs
inclusion body---consisted of replicating initial body and descendant elementary body in the infected cell
classification 1. Chlamydia trachomatis :
(1) biovar trachoma : 14 serotypes(A-K )
(2) biovar lymphogranuloma Venereun(LGV):4 serotypes(L1, L2, L2a,L3 )
(3) biovar mouse
2.Chlamydia pneumoniae: 1 serotype
3. Chlamydia psittaci
Ⅱ
Pathogenicity 1.pathogenic factor :
(1) surface structure :
LPS and MOMP
(2) endotoxin -like substance
2.Disease (1) C.trachomatis
① Trachoma
② Inclusion Conjunctivitis
③ Genital-tract infection –NGU
⑤ Lymphogranuloma Venereun (LGV)(2) C. pneumonia
infantile pneumonia
-------Cheng
MycoplasmaⅠ
yizhe
Introduction1.the smallest free-living prokaryotic organisms that can grow in
artificial media.
2. distributed extensively --Human, animals, plants, insects and sewage.
21
3. Non-cell wall, pleomorphic.
3. pleuro-pneumonia-like organisms—PPLO Ⅱ
Biological properties1. size: 0.2～0.3um,
pass through 0.45filters.polymorphic: coccoid, coccobacillary,Giemsa stain: purpleStructure :
three layer of membrane: two protein membrane, one lipid membrane
terminal structure: some mycoplasma have specialized structures at one or both ends by which they
adhere to respiratory or genital tract mucosal surfaces
5. Propagation pattern: binary fission
6. Both DNA and RNA
7. culturefried-egg colony:
8. classification
(1) Mycoplasmataceae: mycoplasma ,
(2) Acholeplasmataceae
Ureaplasma
(3) Spiroplasmataceae9. Resistant
resistant to penicillin,
polymyxinsensitive to tetracycline,
Ⅲ
Pathogenicity1.M. pneumoniae[MP]
2.Ureaplasma urealyticum [UU]
1.M. pneumoniae[MP] (1)Terminal structure → adherence epithelial
cell, RBC → damage Cell
Membrane →release products (H2O2, toxic enzyme) →toxic enzymetic →injure cell(RBC, tracheal
epithelial cell)
(2)Primary atypical pneumonia [PAP] (a) PAP often in school children and adolescent;(b) Spread by
respiratory, incubation 2~3 weeks; (c) Headache, cough, fever, malaise;
(d) Rarely fetal;(e) Tetracycline
--adolescent,
Erythromycin --children, pregnant women.2.Ureaplasma
urealyticum [UU] (1) genitourinary tract infection—STD
(3) vaginitis,cervicitis→premature birth,
(4) arthritis
(2) nongonococcal urethritis (NGU)
abortion, sterility
Erythromycin,Tetracycline,Doxycycline
-----Cheng
yizhe
22
Rickettsia
Ⅰ Biological properties
1. small G- bacilli, 2. Giemsa stain: violet or blue;3.They are obligated intracellular parasites ;
4. binary fission ;5. have both DNA and RNA;6. Culture:
susceptible animal (guinea pig),
yolk sac of chick embryo,
cell culture;7.
Rickettsiae normally enter the body (mammalian
reservoir) through the bite or
feces of an infected arthropod vector.
Arthropod vector : mite , tick , louse , flea
8. resistance: week, sensitive to antibiotic
9. Antigen: type-specific Ag-- stimulate antibody
10. weil-Felix reaction
Proteins: Proteus strains OX-2, OX-19, OX-K
tilter:>1:160 and progressive rise
11.Classification:(1) Typhus group : Epidemic typhus (R.prowazekii)
Endemic typhus (R. mooseri)
(2) Spotted fever group
(3) Tsutsugamushi group
Epidemic typhus (R.prowazekii)(1) louse-borne ; substandard living condition, poor sanitation;
overwhelming bacterimia
(2) transmitted way
(3) fever(temperature rises to 40℃);
(4) treatment: sanitation, eradication of human lice; vaccine , tetracycline
transmitted way: Rickettsiae →arthropod vector, bite →human skin,wound →multiply in epithelial
cells of small blood vessule →toxin released in the blood →toxemia →many organs →pathogenesis
Endemic typhus(R. mooseri) flea-borne; murine typhus transmitted way :
rat
human louse
23
rat flea
rat louse
rat flea
Human
rat
human
human louse
fever; headach; maculopapular rash
II.Pathogenicity Rickettsiae diseases are transmitted from animal to animal by the bite of an arthropod
vector .Rickettsia disseminated through the bloodstream, enter endothelial cells by induced phagocytosis
escape from the phagosome, intracellular multiply and eventually destroy their host cell
------Cheng
yizhe
Spirochetes
Introductionmonocellular organism , flexible, helical, possess an axial filament (active motile)2.situs is
between bacterium and protozoa
3.general structure : envelope , axial
filament , protoplast
4.sensitive to antibiotics (penicillin etc.)
5.Fontana silver stain:brown
classification:
pathogenic organisms
Borrelia-------B.recurrentis----relapsing
fever Treponema—T.
pallidium----syphilis Leptospira---Leptospirosis, systemic infection
Section I. Leptospira
I. Biological properties
1. Morphology 1) tightly coiled spiral, long (6~12μm) 2)
3) active motility---rhythmic contraction of axial filament 4)
2.culture 1)
grow in artificial medium 2)
hooked in one or both ends
silver-stain
aerobic growth;A
Antigen P Ag (peptidopolysacharides)----
type-specific : 180 serotypes S Ag (lipidosaccharides) -- generous-specific: 19 serotypes
24
II.
Pathogenicity 1.
pathogenic
substance hemolysin-----lysis
RBC
Cytotoxicity
factor-----cytopathogenic effect endotoxin-like component(ELS)------cause fever, inflammation, necrosis
III.
Disease infected
animal → discharge urine → water/soil
→ human skin → blood stream
→septicemia→recovery or fatality(30%)
Clinical type :jaundice—hemorrhage type
influenza—typhoid type
pulmonary—hemorrhage type
renal—failure type
meningoencephalitis type
IV.
Immunity Humoral—immunity; after two weeks, specific Ab can be examed
V.
Treatment and prevention 1.penicillin, tetracycline, streptomycin or erythromycin (in large
enough doses early in the infection) 2.rodent control 3.vaccination of domestic animal
Section 2 Treponema pallidium
I. Biological properties
1.
fine,
culture 4.
long,
tightly
coiled
organism 2.
silver-stain:
brown 3.
difficult
to
sensitive to temperature (41℃ 1hr); dry (1~2hr); soapsuds; penicillin, tetracycline
II. Pathogenicity T. pallidum is the causative agent of syphilis, a common sexually transmitted disease
found world-wide. It is generally transmitted by genital/genital contact. Transmission in utero or during
birth can also occur.
The syphilis(lues) is usually acquired: 1.during sexual contact----venereal disease 2.contact with
mucous-membrane lesions 3.blood transfusion----rare (causative treponema will not survive more than
48 hours under the condition of blood storage)
4.
congenital syphilis---organism pass through the placenta to infect fetus.
Acquired syphilis----sexual contact
*primary syphilis (10-60 days)---- chancre
*secondary syphilis(2-10 weeks later)
*tertiary syphilis(several years later)
Treatment
25
No vaccine exists
antibiotic therapy (usually penicillin G) is usually highly effective.
Actinomyces
1)
.Filamentous prokaryotic microbes, form hyphae 2). Cell structure is similar to bacteria 3).
sensitive to antibiotics
4). Actinomyces colonies ---Sulphur granules
---- cheng yi zhe
26
Individual Virology
Respiratory viruses
Characteristic properties of common respiratory viruses
viruses
Diameter
(nm)
Shape and strecture
Nucleic
Envolope
acid
Influenza
virus
80-120
ssRNA
+
Parainflue-nz
a virus
100-250
ssRNA
+
Measles
virus
120-250
ssRNA
+
Mumps
virus
110-360
ssRNA
+
90-130
ssRNA
+
50-70
ssRNA
15-30
H,N
No.of
serotypes
variable
3
4
H(+)
N(-)
diseases
Influenza, Common
cold,
Bronchitis
Common cold
Croup
Pneumonia
1
Measles, SSPE
1
Mumps,
Menungutis,
Orchitis
1
Bronchiolitis,
Pneumonia
+
1
Postnatal
and
congenital rubella
ssRNA
_
>110
Common cold
80-100
ssRNA
+
>3
Common cold
Reovirus
60-90
dsRNA
_
3
Adenovirus
70-90
dsRNA
_
33
Respirato-ry
syncytial
virus
Rubella
virus
Rhinovirus
Coronavirus
_
Upper resp. tract
infection,
diarrhea
Acute resp. disease,
Pneumonia,
Conjunctivitis
Section 1 Influenza virus
Comprises influenza A,B and C, viruses.
Influenza A viruses can infect a variety of different species (aquatic birds, chickens, horses etc)
and can cause worldwide epidemics of influenza (occur approximately every 10-20years).
Influenza B only infects humans and can cause major outbreaks of influenza.
influenza C mainly infects humans and can cause mild respiratory tract infections ,but does
not cause outbreaks of influenza
ⅠBiological characteristics
27
1.Morphology and structure
Spherical, 100-120nm in diameter, enveloped, spikes
1)core: -ssRNA, segmented(7- 8 pieces )
2) NP: surround and bind the RNA, type-specific, stable.
3) envelope:M1、M2、lipid bilayer membrane
4）spikes：HA、NA
Hemagglutinin ( HA ):
2units: HA1and HA2
* agglutinate human and some animal RBC
* be related to the adsorption of viruses (receptor : neuraminic acid )
* antigenicity: show great variability
Abs to the HA are protective,neutralize viral infectivity.
Neuraminidase ( NA )
* be related to the release of viruses: hydrolyze the terminal neuraminic acid of
glycoprotein on surface of cell.
* antigenicity: variable
2.Type and variation
Based on antigenicity of NP and MP: Influenza A, B, C.
Based on HA, NA: subtype
* Antigenic drift: which are minor changes based on mutations in the genome RNA.
* Antigenic shift: which are major changes based on the reassortment of segments of the
genome RNA.
3.Cultivation
Culture in chicken embryo.
Culture in cell culture (non-CPE)
4.Resistance
Inactivated 56℃ 30min.
ⅡPathogenesis and immunity
*is spread via respiratory droplets.
*virus particles binds to cells of the respiratory epithelium
ⅢClinical features:
*respiratory tract symptoms: sore throat, cough etc;
*systemic symptoms: headache, fever, myalgias (muscle pains).
Ⅳ.Control
Vaccine: Whole inactivated virus vaccines ----including H1N1,H3N2 and a B subtype.
28
Section 2 Avian Influenza
1.Blong to type A influenza viruses;
2.can infect birds, pigs, horses, seals and whales, etc;
3.Avian influenza infections in humans:
1997: Hong Kong, (H5N1)
1999: Hong Kong, H9N2
2003: Hong Kong , H5N1
2003: Netherlands, H7N7
2003: Hong Kong, H9N2
4.serotypes including H5 and H7 are associated with disease in poultry.
Section 3 SARS-associated coronavirus (SARS-CoV)
1.A novel coronavirus;
2.60-220nm, +ssRNA(29.7kb), enveloped;
3.Major structures: N, S, M, E
4.Transmission: close person-to-person contact
5.Associated diseases: Severe Acute Respiratory Syndrome (SARS)
-----Qi
mei
29
Enteroviruses
ⅠClassification:
1)Poliovirus: 3 serotypes
2) Coxsackievirus: Group A and Group 30serotypes
3)ECHO virus:
34 serotype
4)New Enteroviruses : serotype 68.69.70.71.72
ⅡCommon Properties:
1) Spherical , 20-30nm, icosahedral symmetry, nonenveloped, +ssRNA
2)cell culture ( cause CPE)
3) resistance : more stable, resistant to lipo-solvents, pH3-5, resist 56℃ 30min
4)Pathogenesis:virus---enteron--- viremia --- different trarget tissue.
Eg:
Poliovirus: V—enteron –viremia– CNS (anterior horn cells , cytocidal effect)
---cause Poliomyelitis
Coxs. Viruses ( group B ):
V— enteron – viremia –cardiacmuscular
(immunopathological reactions) ---- cause viral myocarditis
5) the virus-neutralizing epitopes reside mainly in VP1, although the actual sites may cover
VP2 and/or VP3
Poliovirus
1. Three serotypes, non-cross reaction
2.fecal –oral tramission ,
3. Cause Poliomyelitis
incubation period : 7 - 14 days (range 3 - 35 days).
Following ingestion---- oropharyngeal and intestinal mucosa( lymphatic system)
a transient viraemia.
CNS following dissemination.
outcomes following poliovirus infection:
Subclinical infection (90 - 95%)
Abortive infection (4 - 8%)
Major illness (1 - 2%)
4.Immunity: neutralization Ab
5. Vaccine: attenuated-live vaccine (Sabin vaccine)
This vaccine uses live attenuated virus that is given by mouth, sometimes as liquid drops in
a sugar cube.
Rotaviruses
1.65-75nm, icosahedral, double-shelld capsids (inner capsid, wheel-like)
2.dsRNA: 11segments,
3.Culture: difficult
4.Type: basic on outer capsid, 7 groups(A-G), most of the human rotavirus are of group A
5.Transmission: fecal-oral route
6.mainly infect young children (6 months-2 years)
-----Qi
mei
30
Hepatitis A-E Viruses
Section 1 Hepatitis A virus ( HAV )

A Picornavirus, now classified as a heptovirus, formerly known as enterovirus 72
ⅠBiological properties
1.spherical, 27nm, icosahedral, non-enveloped
2. +ssRNA, 7400bp.
3. One serotype
4. Chimpanzee and marmoset(绒猴)are susceptible.
5.Culture: difficult, no CPE, grow slowly.
6.Stable: resistance to 60℃ 1h, pH 3; inactivated at 100℃ 5min.
ⅡPathogenesis and immunity
1.Source of infection: patients, subclinical infected person.
2.Transmission: fecal-oral route.(from fecally contaminated water or food)
3.Children are the most frequently infected group
4.Pathogenic mechanism: HAV----mouth----intestine----blood----liver
5.Mechanism of hepatocyte damage:
Cause acute hepatitis.
1) viral direct effect
2) immunol injure
ⅢControl
1.ã-globulin for urgent prevention.
2.Vaccine: inactivated vaccines are commonly used (The virus is grown in human cell culture
and inactivated with formalin).
Section 2 Hepatitis B virus ( HBV )
Globally, more than 300 million people are chronically infected with HBV and about
75% of them are Asian.
ⅠBiological properties
1.structure:
1).partially dsDNA, circular 3200bp
the long strand is complete, variable length of the short strand.
2)layer capsids:
inner capsid: icosahedral, carry HBcAg, HBeAg
outer capsid: carry HBsAg, pre-S Ag.
31
2. Three different particles :
1)Dane particle: intact virion, 42nm.
2)Small spherical particle: 22nm, carry HBsAg.
3)Tubular particle:
consists of HBsAg.
3.Gene and encoded proteins
S, C, P, X regions, located in the long strand.
1)S region: HBsAg, pre-S1 protein, pre-S2 protein.
2)C region: HBcAg,
HBeAg.
3)P region:
DNA polymerase(has both RNA-dependent and DNA-dependent activity).
4)X region: X protein.
-----Qi
mei
32
4.Replication:
There are some parallels between the HBV and the retroviruses.(reverse transcription)
5.Ags & Abs
1)HBsAg: *4 subtypes: adr, adw, ayr, ayw;
ayw predominates in N.Europe, N.America and Australia ;
adr in China and Japan
*4 genetypes: A, B, C, D;
*HBsAg ( + ): indicates that the patient is infected with HBV, either as a recent
acute infection or as a carrier;
*anti-HBs:
protective.
2)pre-S1 Ag and pre-S2 Ag:
* be related to the adsorption of virus;
* enhance the antigenicity of S protein.
*anti-pre-S1: protective, neutralizing Ab
*anti-pre-S2: protective, neutralizing Ab
3) HBcAg:
*not easily detective in serum
*anti-HBc: not protective
*anti-HBc ( + ): viral multiplication, active infection, infectious.
4)HBeAg:
*C gene and preC gene encode HBeAg protein
*Lies in inner capsid and easily detected in serum
*HBeAg ( + ): viral multiplication, active infection, infectious. variable
*anti-HBe: not protective, viral multiplication and active infection are reduced, has less
infectious
5)HBxAg:
associated with cancer.
6.Can not grow in any cell culture.
7.Resistance
stable 60℃1h , 100℃10-15 min.
Ⅱ.Pathogenesis & immunity
1.Source of infection: patients, HBsAg-carrier( Who has HBsAg persisting in their blood for
at least 6 months).
2.Transmission way:
① By blood or blood products;
② Sexual transmission;
③ Vertical transmission: from mother to child(during birth or breast feeding).
3.Mechanism of pathogenesis:
*hepersensitivity reactions ( type Ⅱ, Ⅲ,Ⅳ )
*Variation
HBV preC mutate----HbeAg----immunal escape
33
Ⅲ.Microbiological detection
1.Detecte Ags & Abs:
HBsAg, anti-HBs, anti-HBc, HBeAg, anti-HBe.
2. HBV DNA
HBV-DNA - indicates active replication of virus, more accurate than HBeAg especially in
cases of escape mutants. Used mainly for monitoring response to therapy.
3. Sera DNA polymerase
Ⅳ.Control
1.Vaccination - highly effective recombinant vaccines are now available.
*Serum derived - prepared from HBsAg purified from the serum of HBV carriers
*Recombinant HBsAg - made by genetic engineering in yeasts
2.Treatment
*Interferon –
*Lamividine - a nucleoside analogue reverse transcriptase inhibitor.
Section 3 Hepatitis C virus ( HCV )
1. +ssRNA ,
lipo-enveloped.
2.Can not culture.
3. easy variation.
4. Transmission: transmitted mainly by blood and blood products.
5. HCV is closely related to hepatoma.
6.Microbiological detection: Detect anti-HCV; Detect viral RNA: RT-PCR.
7.Control:Neither active nor passive immunization is available.
Section 4 Hepatitis D virus ( HDV )
1. Spherical, 35-37nm.
2.–ssRNA, circle, 1700bp. Outer capsid is HBsAg.
3.One serotype.
4.Defective virus.
5.Human and chimpanzee are susceptible to HDV.
6.Transmission: same as HBV.
7.Infecious mode:
*Coinfection
– severe acute disease.
– low risk of chronic infection.
*Superinfection
– usually develop chronic HDV infection.
34
– high risk of severe chronic liver disease.
– may present as an acute hepatitis.
8.Detect HDAg & anti-HDV.
Section 5 Hepatitis E virus ( HEV )
1 Spherical, 27-38nm.
2 +ssRNA, 8.5kb.
3 Not stable.
4 Not grow in cell culture.
5 Transmission: fecal-oral route.
6 Mainly involve young and adults.
7 Incubation period: average 40 days.
8 Cause acute hepatitis, 4-6 weeks recovery, no chronic.
9 Mortality 1-2%, pregnant woman 10-20%.
10. Detect viral Ag in faeces:
Detect anti-HEV IgM in serum:
-----Qi
mei
35
Retrovirus
Retroviridae include 3



Oncovirinae:
Lentivirinae:
Spumavirinae:
subfamilies:
HTLV (Human T-cell Lymphotropic Virus)
HIV (Human Immunodeficiency Virus)
Human immunodeficiency virus ( HIV )
*Pathogen of AIDS ( Acquired Immunodeficiency Syndrome ).
*HIV-1 is found worldwide, HIV-2 is found primarily in West Africa.
Ⅰ.Biological properties
1. Spherical, enveloped, spikes.
2. Structure:
*Core: 2 copies of +ssRNA ( to be diploid ); reverse transcriptase;
*Capsid protein: P24
*Matrix protein: P 17.
*Envelope:
gp41:mediates fusion of the viral envelope with the cell membrane,and the virion enters
the cell.
gp120:
1)be associated with adsorption (binding site for
CD4 molecule of T cells).
2)be able to stimulate the production of neutralizing antibodies.
3)easy variation.
3.Genes:
*Structural genes:
gag: coding for capsid proteins ( p17, p24, p7 )
pol: coding for protease that cleaved the various viral precursor proteins,
reverse transcriptase etc.
env: coding for gp120, gp41.
*Regulatory genes:
tat: regulating the synthesis of viral proteins ( + ).(enhance viral gene
transcription)
rev: regulating the synthesis of viral proteins ( + ).
nef: regulating the synthesis of viral proteins ( - ).
*LTR: contain promotor and enhancer sequences.
4.Resistance: 56℃inactivated.
5.Replication:
*absorption :
36
gp120 bind for CD4 molecule of T4 cells the necessary co-receptors (chemokine receptors)
for HIV-1 entry:
CXCR4 (fusion) for T-cell line (T)-tropic strains
CCR5 for macrophage (M)-tropic strains.
*Penetration: membrane fusion
*Uncoating:
*Biosythesis:
RNA---cDNA--- RNA:DNA hybrid molecule ---dsDNA(provirus) integrated into host
DNA--- stay latent ----- enter a productive cycle
*assembly and release:
budding
Ⅱ.Pathogenesis & immunity
1.Infectious source: patients (symptomatic), infectious people(anti-HIV(+),
asymptomatic).
2.Transmission pathway:
1) By blood or blood products;
2) By Sexual contact;
3) Vertical transmission:
from mother to child.
3.Pathogenesis:
* gp120 of HIV select CD4 molecule
of T4 cells ---viruses multiply in T4
cells---cell-mediated immunodeficiency---opportunistic infections and tumors occur---death
*Destruction of T4 cells is achieved by:
① Viral replication
②Syncytium formation via membrane gp120 binding to cell CD4 antigen
③Cytotoxic T cell lysis of infected cells
④Cytotoxic T cell lysis of T4 cells carrying gp120 released from infected cells
⑤ Natural killer cells
⑥ Antibody-dependent cell cytotoxicity.
⑦Induce appoptosis.
4.Clinical features
Exposure---Seroconversion---Asymptomatic---PGL(persistent
generalized
lymphadenopathy,
) or ARC(AIDS-related complex) ---AIDS
a.Opportunistic Infections:
Fungal, Bacterial, Viral
b. Opportunistic Tumours
Kaposi's sarcoma, is observed in 20% of patients with AIDS.
Ⅲ. Diagnosis
1. The detection of the antibody to HIV
2. The detection of viral components or detection of viral
3. Isolation of the virus in culture
RNA
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Ⅳ.Control
1.Vaccines:
Several vaccines are under trial.
2. Treatment
(1.) Nucleoside analogues reverse transcriptase inhibitors. AZT, DDC, DDI and
lamuvidine.
(2.) Non-nucleoside analogue reverse transcriptase inhibitors e.g.
Nevirapine( 抑制
DNA 合成)
(3.) HIV Protease inhibitors e.g. Ritonavir, Indivavir. They are the most potent inhibitors of
HIV replication to date.
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Herpesviruses
Ⅰ.Classification:
Classification and associated diseases of herpesviruses( 表 －)
Classification and associated diseases of herpesviruses
Viruses
Herpes simplex virus 1 ( HSV-1 )
Herpes simplex virus 2 ( HSV-2 )
Varicella-zostervirus ( VZV )
Epstein-Barr virus (EBV )
Cytomegalovirus (CMV )
Human herpesvirus 6 ( HHV 6 )
Clinical illness
Gingivostomatitis
Labial herpes
Keratoconjunctivitis
Herpesencephalitis
Genital herpes
Neonatal herpes
Cervical carcinoma
Varicella
Zoster
Infectious mononucleosis
Burkitt′s lymphoma
Nasopharyngeal carcinoma
Cytomegalic inclusion body disease
Mononucleosis
Congenial deformity
Roseola
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Ⅱ.Common properties
1.Linear dsDNA.
2.120-200nm, Icosahedral , Enveloped .
4.Most can grow in HDC, cause CPE.
5.Various infectious expression:
apparent infection
latent infection
integrating infection
congenital infection
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Human papillomaviruses ( HPV )
1.dsDNA, non-enveloped.
2.Can not culture.
3.More than 80 types have been identified.
4. Pathogenesis:
HPV type 16, type 18 (high-risk type) --- malignant tumor
HPV type 6, type 11 (low-risk type) --- condyloma acuminatum
Arboviruses
Ⅰ.Common properties
1.+ssRNA, icosahedral, enveloped, hemagglutinin.
2.Sensitive to heat, lipo-solvents, acid.
3.Intra-cytoplasmic multiplication, newborn mice are susceptible.
4.Reproduce in arthropods, arthropods are vector and reservoir host.
5.Epidemics with marked geographical and seasonal distribution..
Ⅱ.Diseases caused by arboviruses
1.Encephalitis: e.g. B encephalitis.
2.Systemic infection: e.g. denge fever
3.Hemorrhagic fever: e.g. epidemic hemorrhagic fever.
4.Hepatitis associated infection: e.g. yellow fever.
Rabies virus
1.Bullet shaped
2. –ssRNA, helical symmetry, enveloped.
3. Cytoplasmic inclusions ( Negri bodies ).
4. one serotype.
5.Pathogenesis:
* The cause: bite of rabid animal.
* Incubation period: average 3-8 weeks. (depending on the severity and site of wound )
* viruses ( in saliva of rabid animal )---wound--- never fiber ---CNS --- fatal encephalitis.
6.Control:
* Treat the wound: clean, infiltrate with antirabies serum.
* Vaccines: inactivated vaccines
Hantaviruses
1.cause haemorrhagic fever with renal syndrome (HFRS) or, more recently hantavirus
disease (HVD).
2.Genome consists of 3 stranded segments; L, M, S.
3.At least 6 serotypes are known
4.The virus is found in the lungs, spleen and kidneys for long periods in the rodent,
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perhaps for life.
Saliva appears to play an important role in the horizontal transmission of the virus
between rodents.
5. Transmission (1) through the respiratory route( via aerosols of virus particles excreted by
rodents in their lungs, saliva, urine and faeces. )
(2) bites by rodents.
6. multisystem pathology:
damage to capillaries and small vessel walls, resulting in vasodilation and congestion with
hemorrhages.
Mechanisms: immunopathological mechanisms,
viral cellular
destruction.
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Prion
ⅠDefinition:
A protein particle that is capable of causing an infection or disease. Like viruses, prions
are not capable of reproduction by themselves. Unlike viruses, prions do not contain genetic
material (DNA or RNA).
ⅡThe prion protein PrP exists in two different conformational forms.
*PrPc is thought to be the benign form of the protein and is found in normal, healthy cells.
*PrPsc is thought to be the infectious "scrapie" form which causes neurodegenerative
diseases such as bovine spongiform encephalopathy (BSE), Creutzfeldt-Jakob disease (CJD),
kuru, and Gerstmann-Straussler syndrome.
Ⅲ.Human prion diseases:
Form
Phenotype (Clinical & pathological features)
Sporadic
Creutzfeldt-Jakob disease (CJD), Familial insomnia (FI)
Familial
Creutzfeldt-Jakob disease (CJD), Fatal Familial Insomnia
(FFI), Gerstmann-Sträussler-Scheinker Syndrome (GSS)
Acquired
Creutzfeldt-Jakob disease (CJD), Kuru, new variant
Creutzfeldt-Jakob disease (nvCJD)
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