Transcript Gram Negative Bacteria

Gram Negative Bacteria
Enterobacteriaceae
2
Infections associated
with
Enterobacteriaceae
Fig. 30-1
3
Enterobacteriaceae
 Gram negative rods
 most are motile (peritrichous flagella)
 most are encapsulated
 LPS is a virulence factor
 many have “serum resistance”
 inhibitions of complement proteins (Ab’s can’t attack)
 Associated with:
 Enteric (GI) infections
 Bacteremia (bacteria in the blood)
 UTIs (urinary tract infections)
4
Diarrhea
 ~1 billion people worldwide suffer from acute diarrhea
at least once/year
 5-8 million deaths/year
 primarily in developing nations
 ~100 million infections in U.S.
 250,000 require hospitalization
 3000 die
 90% of acute diarrhea caused by infectious agents
 fecal-oral contamination
5
High risk groups in U.S.
 Travelers – 40% of tourists to Latin America, Africa, Asia
develop “traveler’s diarrhea”






ETEC – enterotoxigenic E. coli
Shigella
Salmonella
Campylobacter
Giardia (Russia, camper’s, swimmers)
Cyclospora (Nepal)
 Consumers of certain foods
 Chicken, mayonnaise, creams, eggs: picnic, banquet,




restaurant (Salmonella, Campylobacter, Shigella)
Hamburger: undercooked (EHEC – enterohemorrhagic E. coli)
Fried rice (B. cereus)
Seafood (Salmonella, Vibrio, hepatitis A)
Fermented tofu (C. botulinum)
 Immunocompromised
6
High risk groups in U.S. (cont.)
 Daycare participants and their family
 Shigella
 Giardia
 Cryptosporidium
 rotavirus
 Institutionalized persons
 Nosocomial (acquired in a hospital) infections of hospital
patients
 Clostridium difficile
7
Treatment - gastrointestinal disease
 Fluid/electrolyte replacement
 fluid alone for mild cases
 dehydration most common cause of death due to diarrheal
disease
 Antibiotics
 not used unless systemic/severe
 e.g.
enteric fever
 immunosuppressed
 Antibiotic prophylaxis for those traveling to
high-risk countries (esp. immunocompromised)
8
Enteric infections
 Overview of symptoms
 non-inflammatory
 nausea
 vomiting
 diarrhea
 inflammatory
 Dysentery (severe diarrhea containing mucus
and/or blood)
 Invasive (systemic)
 Typhoid Fever (enteric fever)
9
“Common” organisms associated with enteric
infections
I
Mechanism: Non-inflammatory
II
(enterotoxin)
(invasive, cytotoxin)
Penetrating
(invasive, spread)
Location:
proximal small bowel
colon
distal small bowel
Illness:
Diarrhea
Dysentery
Enteric fever
blood, fecal PMNs
(polymorphonuclear
leukocytes =
neutrophils)
fecal mononuclear
leukocytes
(monocytes,
lymphocytes)
Shigella
Invasive E. coli
S. enteritidis
C. difficile
E. histolytica
B. coli
S. typhi
Y. enterocolitica
Stool exam: no fecal leukocytes
Example
organisms:
V. cholerae
E. coli
Salmonella
Campylobacter
Giardia
Cryptosporidium
Rotavirus
Norwalk-like agents
Inflammatory
III
10
Pathogenicity of enteric bacteria
 Host factors
 personal hygiene
 fecal-oral contamination
 gastric acidity
 enteric microflora
 specific immunity
11
Pathogenicity of enteric bacteria (cont.)
 Microbial factors
 Toxins
 Neurotoxins



usually ingested as preformed toxins
Staphylococcal toxins (Staph. aureus)
Botulinum toxin (Clostridium. botulinum)
 Enterotoxins



having a direct effect on intestinal mucosa (elicit fluid secretions)
Cholera toxin (Vibrio. cholerae)
E. coli toxins
 Cytotoxins





mucosal destruction (often see dysentery)
Shigella dysenteriae
Clostridium perfringens
S. aureus
Clostridium difficile
12
Enterobacteriaceae
Ubiquious (they are everywhere) - soil, water,

vegetation, normal intestinal flora

~40 genera, 150 species
Gram negative, facultative anaerobic rods
oxidase negative - no cytochrome oxidase
members of family commonly associated with
human disease:










Escherichia
Salmonella
Shigella
Yersinia
Klebsiella
Serratia
Proteus
13
Enterobacteriaceae pathogens
associated with opportunistic infections






septicemia
pneumonia
meningitis
urinary tract infections (UTI)
can be primary pathogens (unrelated to immune
status)
14
Enterobacteriaceae and disease
http://www.ratsteachmicro.com
15
Lab identification of the enterics
http://class.fst.ohio-state.edu
www.mc.maricopa.edu
Green sheen; black nucleated centers
MacConkey agar
selective and differential
EMB agar
selective and differential
16
Yellow = sugar fermentation
Black = H2S positive
Air bubble = gas production
TSI
17
Salmonella-Shigella differentiation
 Salmonella-Shigella agar (SS agar)
 Hecktoen agar – inhibits most Gram +, various sugars to
judge fermentation (fermenters – red/orange; non-fermenters –
green), H2S production (black)
Note: Shigella is a
non-fermenter, H2SK. pneumoniae (L); M. luteus (R)
S. typhimurium (L); P. vulgaris (R)
H2S production (black ppt)
www.austincc.edu/microbugz/
18
E. coli and the serotypes

Lactose positive

note: many intestinal pathogens are lactose negative


ex. Salmonella, Shigella, Yersinia
grouped based on surface antigens
(serotypes)
 O antigen (lipopolysaccharide)
 H antigen (flagellar)
 K antigen (capsular)


O157:H7 (EHEC – enterohemorrhagic E. coli)
O148:H28 (ETEC – enterotoxigenic E. coli)
19
E. coli serotype differentiation
1. immunologic assay
2. growth on MacConkey agar with sorbitol (SMac)
 most E. coli can ferment sorbitol (form pink colonies)
 E. coli O157:H7 does not ferment sorbitol (colonies
are clear/colorless)
www.komed.com
20
E. coli pathology
 most strains of the pathogenic E. coli are capable of
pathology only within the intestinal tract (some
exceptions)
 most pathogenic strains associated with disease in
developing countries (except EHEC is common in
the USA)
 dependent upon strain, different disease
severity/symptoms (e.g. pathotype)
21
E. coli pathology (cont.)
 pathogenic strains produce virulence factors
 found on:
 Plasmids (a DNA molecule that is separate from, and can
replicate independently of, the chromosomal DNA)
 Bacteriophages (viruses that infect bacteria)
 virulence factors include:
 Fimbriae (allow bacteria to stack up on each other to shelter
themselves from immune system
 secretion systems (the process of toxin release)
 toxins
22
E. coli strains/serotypes
 most normal flora E. coli are non-pathogenic in
intestinal tract
 pathogenic strains:
 EPEC (enteropathic)
 ETEC (enterotoxic)
 EHEC (enterohemorrhagic)
 EIEC (enteroinvasive)
 EAEC (enteroaggregative)
 UPEC (uropathogenic)
23
Enteropathogenic E. coli (EPEC)
destruction of surface microvilli (small intestines)
•fever
•diarrhea (infantile)
•malabsorption of fluids
•vomiting/nausea
•hard to replace fluids
•non-bloody stools
common in developing countries (rare in U.S.)
http://www.annauniv.edu/biotech/epec.jpg
24
EPEC pathology - diarrhea
 since this is primarily a disease of the young (less
the 6 months old), fluid replacement is important
 intense vomiting - i.v. fluids are usually required
 disease self-limiting (antibiotics usually not required)
 breast feeding seems to have a strong protective
effect
 IgA and other factors decrease bacterial attachment
25
Enterotoxigenic E. coli (ETEC)
“Traveler’s diarrhea”
primarily in developing nations

~650 million cases/year
~80,000 in travelers from the U.S.


Two types of toxins


heat labile toxins (LT)

similar to cholera toxin (although not as severe)
 lack of absorption of fluids = watery diarrhea

heat stabile toxins (ST)

no inflammation, self-limiting
26
Enterotoxigenic E. coli (ETEC)
many different ETEC strains


disease is self-limiting


watery diarrhea common symptom
exposure provides immunity


adults living in endemic areas, often immune
children, through exposure to the many strains, eventually
develop immunity
therapy




fluid replacement
bismuth subsalicylate tablets (Pepto-Bismol, etc.)
provide antibiotics to travelers in the event they get sick
while abroad
27
Enterohemorrhagic E. coli (EHEC)
usually O157:H7
many different types of E. coli



identifying O157:H7…finding a slightly different hay in a
large haystack.
strain must have virulence/toxin genes.
Vero toxin (VTEC) = “shiga-like” toxin (cytotoxin)




aka Shiga toxin-producing E. coli (STEC)
AB toxin

“A” inactivates 28S rRNA = stop protein synthesis
 death of epithelial cells
28
EHEC

~75,000 cases in U.S./year


estimated that only ~100 cells can cause
infection



~60 deaths
many EHEC serotypes (~50)
in U.S., most diseases due to 0157:H7
disease can be mild to severe (hemorrhagic
colitis = bloody diarrhea)


depends on strain
patient status (age, physiological status)
29
EHEC symptoms
 Hemorrhagic (hemorrhagic coilitis)
 bloody, copious diarrhea
 few leukocytes
 afebrile (no fever)
 usually self limiting (in ~1 week)
 Hemolytic Uremic Syndrome (HUS)
 hemolytic anemia
 thrombocytopenia
 kidney failure
 5-10% of kids infected with
EHEC
30
EHEC
cattle seem to be the major reservoir


humans become infected by ingesting undercooked
meat (beef), unpasteurized milk, fruits and fruit juices
(fecal-contaminated fruit), uncooked vegetables
detection: 0157 strains do not ferment sorbitol (or do
so slowly)


follow up with serological/biochemical testing to confirm
therapy


supportive therapy
31
Enteroinvasive E. coli (EIEC )
dysentery




resembles shigellosis (Shigella dysenteriae)
relatively rare in U.S.
common strains: O124, O143, O164


need relatively large inoculum: 108-1010
invade and destroy colonic epithelium



usually causing watery diarrhea
some patients will progress to dysentery
organism replicates within cytoplasm of cell
32
Enteroaggregative E. coli (EAEC )
associated with persistent watery diarrhea





> 14 days (especially infants)
traveler’s diarrhea – maybe as important as ETEC
fimbriae allow for bacteria to stack up on each
other
bacteria stimulate
mucous production called
biofilm formation
(bacterial community)
33
Uropathogenic E. coli (UPEC)
 most common cause of UTIs
 females more than males
 some serotypes have pili that preferentially binds
to uroepithelial cells
34
Salmonella

Gram negative bacilli, lactose negative
motile, H2S gas production (some exceptions)

~2500 serotypes!

often, the serotypes are considered to be
individual species
 nomenclature is a “mess”

35
Salmonella

S. choleraesuis is the “major” species

organism that causes enteric fever:

S. choleraesuis ssp. choleraesuis, serovar typhi
often just called: S. typhi
 Better designation: Salmonella Typhi

 S. enterica ssp. enterica serotype
typhimurium is shortened to
S. typhimurium (Salmonella Typhimurium)
36
Salmonella subtyping

Serotypes based on:
 O antigen (LPS outer sugars)
 surface Vi antigen (only in some sub-
types)
 capsule antigens (vi = virulence antigens)
 flagella H antigens

most clinical labs divide Salmonella into serogroups
(A, B, C1, C2, D, and E) based on O-antigen antisera
37
Salmonella infection

human intestinal disease due to ingestion of
bacteria (contaminated food/water)
organism gets to small intestines
 macrophages often ingest bacteria
 bacteria are then protected from host responses
(e.g. complement, antibodies, etc)


Salmonella alters host cells:


changes host cell to allow for “bacteria-mediated
endocytosis (absorbing a substance from outside
the cell)”
prevents lysosomal enzymes of macrophage from
degrading bacteria
38
Salmonella pathology

bacteria is disseminated by macrophages to:


liver, spleen, lymph nodes, bone marrow
systemic symptoms likely due to host
response against pathogen

inflammatory cytokines secreted by activated
macrophages. Cytokines are chemicals that call
other WBCs to come to the area.
39
Salmonella pathology (cont.)
non-typhoid and typhoid Salmonella
infections



typhoid relatively rare in U.S., although 21 million
infections worldwide (~200,000 deaths)
non-typhoid Salmonella much more common
 human acquire infections from poultry/eggs,
dairy, and contaminated work surfaces
(cutting boards)
 in U.S., ~40,000 reported cases (estimated 2
million)
40
Enteric (typhoid) fever


systemic disease caused by S. Typhi or S.
Paratyphi
originally called typhoid fever because of some
similarities to typhus (fever, nausea, rash, and
other systemic symptoms)



different bacteria, different mechanism of spread
“better name” is enteric fever
disease from ingesting contaminated food



humans only known hosts of these strains
endemic (commonly occuring) in developing nations
not common in U.S. (food/water/sewage care)
41
Enteric (typhoid) fever (cont.)
~70% of U.S. cases obtained from international
travel
infectious dose is low (~103 versus 106-108 for
infections with other species of Salmonella)
Clinical manifestations







febrile illness
disease more severe by S. typhi as compared to S.
paratyphi
after 10-14 days of initial infection, patients have
gradually increasing fever, headache, myalgia (muscle
pain), malaise (fatigue).
at around 21 days after infection, GI symptoms present
(not seen in all patients) – diarrhea
42
Mary Mallon (right) in
1931.
First diagnosed as carrier
in 1907. Quarantined and
then released in 1910.
Went back to work as a
cook in 1914 at a NYC
hospital.
Quarantined permanently
to North Brother island in
1915.
43
www.pbs.org
Diagnosis and treatment of typhoid fever

culture of S. Typhi/S. Paratyphi from patient
blood


problem because of variable numbers of bacteria
throughout the infection
positive diagnosis can be accomplished from stool,
urine, or bone marrow culture


stool culture is often negative in 60-70% early in infection
some strains of S. Typhi have been shown to
be MDR (multidrug resistant)


check for antibiotic susceptibility
carrier state requires ~6 week therapy

if patient has kidney/gall stones, need surgery as well as
antibiotic therapy
44
Gastroenteritis

acute gastritis is characterized by vomiting,
abdominal pain, fever, and diarrhea (many causes)

Gastroenteritis caused by Salmonella:
S. Typhimurium, S. enteritidis, etc. (~200

serovariants)





many animal reservoirs (hard to control)
symptoms often within 8-24hr after ingestion
often self limiting
diarrhea can be mild to very severe (watery,
green, offensive)
symptoms usually last 2-3 days (can be up
to 1 week)
45
Salmonellosis

outbreaks in U.S.

attributed to chicken eggs, processed foods,
and vegetables and fruits (fruit juices)


fecal contaminants
exposure to pets (especially reptiles)
~90% of reptiles carry the bacteria
 1970s – 14% of human cases of salmonellosis
attributed to exposure to turtles
 birds, rodents, dogs, and cats are also potential
reservoirs

46
Salmonellosis diagnosis and treatment
 stool culture

sent to public health departments for phage
typing


mechanism to identify serotype/serovar
disease generally self-limiting
replace fluids/electrolytes if needed
 antibiotics for infants, elderly,
immunocompromised, and those with bacteremia
 many antibiotic resistant strains

vaccine for those traveling to endemic areas
(especially those going camping)

47
Shigella
 causes acute infectious inflammatory colitis
(colon infection)
 aka – bacillary dysentery
 not all infected develop dysentery
 Gram negative rod (bacillus), non-motile
 lactose negative (S. sonnei is a weak fermenter)
 H2S negative
 genetically similar to Esherichia
 Shigella are thought to be serotypes of E. coli
 historically names have not been changed
48
Shigella
 4 main species, different serotypes within each
species (47 serotypes)
 S. dysenteriae (Group A) – most pathogenic
 S. flexneri (Group B)
 most common cause of shigellosis in developing nations
 S. boydii (Group C) - India
 S. sonnei (Group D) – U.S.
 most common cause of shigellosis in industrial world
 mildest
49
Shigella
 ~200 million cases worldwide
 ~1 million deaths (especially among children)
 ~15,000 cases reported/year in U.S. (real number is
higher - ~500,000/year?)
 pathogen of humans and higher primates
 infection from fecal-oral transmission from infected
humans
 highly communicable (need only ~200 cells to
produce disease)
 high rate of secondary household transmission
50
Shigella pathology
 Clinical manifestation
 abdominal cramps, diarrhea, fever, bloody stools
 large numbers of WBC in stool
 inflammatory damage to intestinal epithelium
 Diagnosis
 standard microbiological testing (selective/differential
media: MacConkey followed by SS or Hektoen-enteric,
etc)
 Therapy
 most cases self-limiting
 antibiotic therapy for those with severe symptoms
 because of high rate of spread, all patients should be treated
51
Shigella pathology
 virulence proteins cause “ruffling” of epithelial
cells
 allows for endocytosis of the bacteria
 actin rearrangement allows for cell-to-cell spread
 S. dysenteriae produces shiga toxin (similar to
EHEC)
52
Yersinia
 Enteric pathogens: Y. enterocolitica, Y.
pseudotuberculosis
 Y. pestis – plague (fleas and rats)
 Gram negative, pleomorphic rods
 primarily found in animals (rodents, swine, cattle,
etc) – all are zoonotic diseases
Y. enterocolitica
53
www.emedicine.com
Y. pestis
 Bubonic and Pneumonic plague
 formation of bubos
 bacteria resists phagocytosis
 painful inflammatory lesions
 Pneumonic plague – high mortality (90%
of untreated)
 highly infections
54
Y. enterocolitica (and Y. pseudotuberculosis)
 Y. enterocolitica more common than other enteric
Yersinia sp.
 acute enterocolitis
 mesenteric lymphadenitis (can mimic appendicitis)
 over 60 different serotypes
 serotypes 3, 8 and 9 account for most human infections
 ingestion of contaminated food/milk (can grow at
lower temperatures, 4°C)
 associated with a blood transfusion septicemia
55
Y. enterocolitica transmission
bold lines = common
spread
56
Yersinia
 Diagnosis for Yersinia
 isolation of organism from stool or blood sample
 may need to do “cold enrichment”
 growth at 4-7°C for 28 days with weekly subculture on SS agar
 Therapy
 Plague
 antibiotics (control rodent population)
 Enteric infections: often self-limiting (except if
progress to septicemia)
57
Diarrhea pathobiology, #1
Agent
Incubation
period
Vomiting
Abdominal
pain
Fever
Diarrhea
Toxin producers
B. cereus
S. aureus
C. perfringens
1-8h
8-24h
3-4+
1-2+
0-1+
3-4+, watery
8-72h
2-4+
1-2+
0-1+
3-4+, watery
1-8d
0-1+
1-3+
0-1+
3-4+, watery
Enterotoxin
V. cholera
ETEC
K. pneumoniae
Enteroadherent
EPEC
EAEC
Giardia
Cryptosporidium
Helminths
58
Harrison’s principles of internal medicine, 2005
Diarrhea pathobiology, #2
Agent
Incubation Vomiting Abdominal
period
pain
Fever
Diarrhea
Cytotoxin
producers
C. difficile
1-3d
0-1+
EHEC
59
12-72h
3-4+
1-2+
1-3+, usually
watery,
occasional
bloody
1-3+, initially
watery, quickly
bloody
Diarrhea pathobiology, #3
Agent
Incubation
period
Vomiting
Abdominal
pain
Fever
Diarrhea
1-3d
1-2+
2-3+
3-4+
1-3+,
watery
moderate
inflammation
Salmonella
Camylobacter
V. parahaemolyticus
Yersinia
12h-11d
0-3+
2-4+
3-4+
1-4+,
watery or
bloody
severe inflammation
Shigella
EIEC
E. histolytica
12h-8d
0-1+
3-4+
3-4+
1-2+,
bloody
Invasive
minimal
inflammation
Rotavirus
Norwalk agent
60
Neisseria
 two major pathogenic species
 N. gonorrheae
 associated with STDs
 N. meningitidis
 associated with respiratory and CNS
infections
61
Microbiology/Pathology
 Gram-negative intracellular diplococcus
 infects mucus-secreting epithelial cells
 Oxidase positive
 evades host response through alteration of
surface structures
62
Neisseria gonorrhoeae with pili
Oxidase Positive
In vitro growth
 Obligate aerobes
 Sensitive to drying (“delicate”) and some products in
blood (that is why one uses “Chocolate agar” for
culture
 called fastidious
 Out-competed by normal flora so grow in presence
of select antibiotics (Thayer-Martin agar)
 Need 5% CO2
Endotoxin
 LPS - lipopolysaccharide
 Lipid A, core sugars, outer sugars
 LOS - lipooligosaccharide
 Lipid A, core sugars
 present in Neisseria
NG: Incidence and Prevalence
 Significant public health problem in U.S.
 Number of reported cases underestimates incidence
 incidence remains high in some groups defined by
geography, age, race/ethnicity, or sexual risk behavior
 Increasing proportion of gonococcal infections caused
by resistant organisms
67
Gonorrhea — Rates by state: United States and
outlying areas, 2006
6 7 .3
2 0 .7
1 0 .4
2 4 .0
4 0 .1
6 4 .4
1 4 .4
4 7 .3
1 2 5 .1
2 3 .6
8 1 .5
1 1 5 .6
3 6 .0
9 3 .4
7 9 .2
8 0 .5
6 6 .3
9 2 .2
1 6 7 .4
1 5 8 .12 3 9 . 2
5 2 . 58 5 . 6
1 7 5 .9
8 9 .9
1 3 9 .5
1 9 9 .4
1 6 2 .6
1 5 4 .9
2 4 2 .5
R ate per 100,000
population
2 3 4 . 02 1 6 . 8
2 5 7 .1
1 3 3 .2
6 9 .4
<=19.0
(n= 5)
19.1-100.0 (n= 27)
2 4 0 .6
9 4 .9
11.6
13.7
38.0
47.2
74.4
63.0
176.0
130.8
342.8
7 8 .5
G uam 58.1
1 0 0 .2
9 0 .7
1 5 4 .9
VT
NH
MA
RI
CT
NJ
DE
MD
DC
1 3 4 .8
>100
Pu e rto Ri c o 7 .7
Vi rg i n Is . 3 1 .3
Note: The total rate of gonorrhea for the United States and outlying areas
(Guam, Puerto Rico and Virgin Islands) was 119.4 per 100,000 population.
The Healthy People 2010 target is 19.0 cases per 100,000 population.
(n= 22)
Men
750
Rate (per 100,000 population)
600
450
300
150
0
6.3
279.1
Age
10-14
0
Women
150
300
605.7
25-29
185.7
294.9
30-34
130.8
125.5
35-39
93.5
40-44
53.0
117.1
45-54
65.7
33.9
12.9
18.4
55-64
2.9
4.2
65+
0.7
Total
750
647.9
20-24
320.9
600
35.1
15-19
454.1
450
124.6
Transmission
 Efficiently transmitted by:





Male to female via semen
Female to male urethra
Rectal intercourse
Fellatio (pharyngeal infection)
Perinatal transmission (mother to infant)
 Gonorrhea associated with increased transmission of
and susceptibility to HIV infection
70
Virulence Factors of Gonococcus
 Pilus
 Phase variation and Antigenic variation (of pilus
and opacity protein)
 phase variation – differences in colony appearance
 antigenic variation – varying pili antigenic type
 development of a vaccine will be difficult
 Endotoxin (LOS)
 IgA protease – cleaves at hinge region
 Serum resistance
Gonorrhea: Gram Stain of
Urethral Discharge
72
Source: CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides
Neutrophils Containing Neisseria
biology.clc.uc.edu/Fankhauser/Labs/Microbiolo...
Genital Infection in Men
 Urethritis – inflammation of urethra
 typically purulent or mucopurulent urethral discharge
 asymptomatic in 10% of cases
 Epididymitis – inflammation of the epididymis
 unilateral testicular pain and swelling
 infrequent
74
Genital Infection in Women
 most infections are asymptomatic
 Cervicitis – inflammation of the cervix
 non-specific symptoms: abnormal vaginal discharge,
intermenstrual bleeding, dysuria, lower abdominal pain,
or dyspareunia
 clinical findings: mucopurulent or purulent cervical
discharge, easily induced cervical bleeding
 50% of women with clinical cervicitis have no symptoms
 Urethritis – inflammation of the urethra
75
Complications in Women
 Pelvic Inflammatory Disease (PID)
 may be asymptomatic
 may present with lower abdominal pain, discharge,
dyspareunia, irregular menstrual bleeding and fever
 Fitz-Hugh-Curtis Syndrome
 Perihepatitis
76
Syndromes in Men and Women
 Conjunctivitis
 usually autoinoculation in adults
 symptoms/signs: eye irritation with purulent conjunctival
exudate
 Disseminated gonococcal infection (DGI)
 systemic gonococcal infection
 occurs infrequently. More common in women than in men
 associated with gonococcal strain that produce bacteremia
without associated urogenital symptoms
 clinical manifestations: skin lesions, arthralgias, arthritis,
hepatitis, myocarditis, endocarditis, meningitis
77
Gonococcal Ophthalmia
78
Source: CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides
Disseminated
Gonorrhea—
Skin Lesion
79
Source: CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides
Septic
Arthritis
www.learningradiology.com/images/boneimages1/...
Gonorrhea Infection in Children
 Perinatal: infections of the
conjunctiva, pharynx, respiratory
tract
 ophthalmia neonatorum
 silver nitrate, antibiotics
 Older children (>1 year):
considered possible evidence of
sexual abuse
81
Diagnostic Methods
• Culture tests
– Advantages: antimicrobial susceptibility can be performed
(Chocolate agar/Thayer-Martin)
82
Reporting
 Laws and regulations in all states require that
persons diagnosed with gonorrhea are reported
to public health authorities by clinicians, labs, or
both.
83
Meningococcus
Capsule
meningitisuk.org
Diseases caused by N. meningitidis
 Meningococcal meningitis
 Meningococcemia, sepsis
Virulence Factors of Meningococcus
 Polysaccharide capsule
 Endotoxin (LOS)
 IgA protease
 Serum resistance
Control of Meningococcus
 Vaccine
 does not display same types of phase/antigenic
variation as seen in NG
 Antimicrobials
 somewhat susceptible to penicillins (although some
degree of resistance reported)
Vibrio
 Members of this genus share many characteristics with enteric
bacteria such as Escherichia and Salmonella
 Found in water environments worldwide
 Vibrio cholerae is the most common species to infect humans
 Causes cholera
 Humans become infected with V. cholerae by ingesting contaminated
food and water
 Found most often in communities with poor sewage and water
treatment
Vibrio
 A large inoculum is required to cause disease because the bacteria
are susceptible to the acidic stomach environment
 Cholera toxin is the most important virulence factor of V. cholerae
Cholera Pathology
 Some infections are asymptomatic or cause mild diarrhea
 Can cause severe disease resulting in abrupt watery diarrhea and
vomiting
 “Rice-water stool” is characteristic
 Results in severe fluid and electrolyte loss
 Can progress to coma and death
Diagnosis, Treatment, and Prevention
 Diagnosis
 Usually based on the characteristic diarrhea
 Treatment
 Fluid and electrolyte replacement
 Antimicrobial drugs are not as important because they are lost in the
watery stool
 Prevention
 Adequate sewage and water treatment can limit the spread of V.
cholerae
Campylobacter jejuni
 Likely the most common cause of gastroenteritis in the United
States 5-7% of cases
 Many animals serve as reservoirs for the bacteria
 Humans become infected by consuming contaminated food, milk,
or water
 Poultry is the most common source of infection
 Infections produce dysenteri and frequent diarrhea that is self-
limiting
 Spread of the bacteria can be reduced by proper food handling and
preparation
Pathophysiology
 Transmission
 fecal-oral, person-to-person sexual contact, unpasteurized raw
milk and poultry ingestion, and waterborne Exposure to sick
pets, especially puppies
 infectious dose is 1000-10,000 bacteria
 incubation period of up to a week
93
Disease
– Patients may have a history of ingesting inadequately cooked poultry,
unpasteurized milk, or untreated water.
•
The incubation period is 1-7 days and is probably related to the dose of organisms ingested.
– A brief prodrome of fever as high as 40°C
– headache, and myalgias lasting up to 24 hours
– crampy abdominal pain (abdominal pain and tenderness may be localized)
•
Pain in the right lower quadrant may mimic acute appendicitis (pseudoappendicitis).
– Up to 10 watery, frequently bloody, bowel movements per day
– Patients with C jejuni infection who report vomiting, bloody diarrhea, or
both tend to have a longer illness and require hospital admission.
94
Helicobacter pylori
 Slightly helical, highly motile bacterium that colonizes the
stomach of its hosts
 Causes most (if not all) peptic ulcers
 H.pylori produces numerous virulence factors that enable it to
colonize the stomach
 Many people have this organism in their stomach, but don't get
an ulcer or gastritis.
 Coffee drinking, smoking, and drinking alcohol increase your risk for
an ulcer
Symptoms
 If you are a carrier of H. pylori, you may have no
symptoms.
 May cause cancer
 If you have an ulcer or gastritis, you may have some of
the following symptoms:
 Abdominal pain
 Bloating and fullness
 Dyspepsia or indigestion
 Feeling very hungry 1 to 3 hours after eating
 Mild nausea (may be relieved by vomiting)
96
Diagnosis
 Simple blood, breath, and stool tests can determine if you are
infected with H. pylori.
 The most accurate way to diagnose is through upper endoscopy of
the esophagus, stomach, and duodenum.
 Because this procedure is invasive, it is generally only done on people suspected to
have an ulcer, or who are at high risk for ulcers or other complications from H. pylori,
such as stomach cancer.
 Risk factors include being over 45 or having symptoms such as:
 Anemia
 Difficulty swallowing
 Gastrointestinal bleeding
 Unexplained weight loss
97
Treatment
 Patients who have H. pylori and also have an ulcer are most likely to
benefit from being treated.
 Patients who only have heartburn or acid reflux and H. pylori are
less likely to benefit from treatment.
 The treatment does not work in all patients.
 Treatment must be taken for 10 to 14 days. Medications may
include:
 Two different antibiotics
 Proton-pump inhibitor,
 Bismuth subsalicylate (Pepto-Bismol)
98
Haemophilus
 Small, pleomorphic bacilli
 Obligate parasites due to their requirement of heme and NAD+ for
growth
 Colonize the mucous membranes of humans and some animals
Haemophilus influenzae
 Most strains have a polysaccharide capsule that resists
phagocytosis and is used in classification of the bacteria
 H.influenzae type b is the most significant
 Was the most common form of meningitis in infants prior to the use of
an effective vaccine
 Can cause a number of other diseases in young children
 Use of the Hib vaccine has eliminated much of the disease caused by
H.influenzae b
 Other strains still cause a variety of diseases
101
Other Species of Haemophilus
 H. aegypticus
 Causes conjunctivitis with pus
 H.ducreyi
 Causes a sexually transmitted disease
 Results in the formation of a genital ulcer called a chancroid
 Often asymptomatic in women but in men the chancroid is often
painful
 H.aphrophilus causes a rare type of endocarditis
 Other species primarily cause opportunistic infections
Bordetella
 Small, aerobic, nonmotile coccobacillus
 B. pertussis is the most important
 Causes pertussis, also called whopping cough
 Most cases of disease are in children
 Produce various adhesins and toxins, including pertussis toxin, that
mediate the disease
 Bacteria are first inhaled in aerosols and multiply in epithelial cells
 Then progress through three stages of disease
Stages
 Catarrhal
 Paroxymal
 Convalescence
104
Bordetella
 Clinical significance
 B. pertussis – causes whooping cough
 Acquired by inhalation of droplets containing the organism
 The organism attaches to the ciliated cells of the respiratory tract.

During an incubation period of 1-2 weeks, the organism multiplies and starts
to liberate its toxins.
Catarrhal
 Pertussis toxin
 Has one A subunit (toxic part), plus five different kinds of B subunits
(involved in binding).
Catarrhal
 The increase in cAMP from the combined effects of pertussis
toxin and bacterial adenylate cyclase inhibits host cell
phagocytic cell responses and the inhibition of natural killer cell
activity.
 Dermonecrotic toxin –released upon cell lysis causing strong
vasoconstrictive effects.
Catarrhal
 Trachael cytotoxin – is related to the B. pertussis peptidoglycan.
 might contribute to the killing and sloughing off of ciliated cells in the
respiratory tract.
 Lipooligosaccharide has potent endotoxin activity.
Paroxymal
 Lasts 4-6 weeks.




The patient has rapid, consecutive coughs with a rapid intake of air between
the coughs (has a whooping sound).
mucous has accumulated, and the patient is trying to cough up the mucous
accumulations.
The coughs are strong enough to break ribs!
Other symptoms due to the activity of the released toxins include:
o Increased peripheral lymphocytes
o Metabolic alteration such as increased insulin release and the resulting
hypoglycemia
o Increased capillary permeability and increased susceptibility to
histamine, serotonin, and endotoxin shock
Convalescence
 Symptoms gradually subside.
This can last for months.
 B. pertussis rarely spreads to other sites, but a lot of damage may occur,
such as CNS dysfunction which occurs in ~10 % of the cases and is due to
an unknown cause.
 Secondary infections such as pneumonia and otitis media are common.

Bordetella
 B. parapertussis – causes a mild form of whooping cough
 B. bronchoseptica
 Widespread in animals where it causes kennel cough.
 Occasionally causes respiratory or wound infections in humans.
 Current treatment
 Erythromyin – only effective in early stages of the disease
before the toxin(s) have been released
 Vaccination P part of DPT (killed, encapsulated organism); a
subunit vaccine has also been developed (purified pertussis
toxin).
Diagnosis, Treatment, and Prevention
 Diagnosis
 Symptoms of pertussis are usually diagnostic
 Treatment
 Primarily supportive
 Antibacterial drugs have little effect on the course of the disease
 Prevention
 Immunization with the DPT vaccine
 Cases in the United States have increased due to a refusal by some
parents to have their children immunized
Francisella
 Classification – only 1 pathogenic species – F. tularensis
 Morphology and cultural characteristics
 Minute, pleomorphic g- rod that stains poorly
 Staining may be bipolar
 Nonmotile
 Nonencapsulated
 Won’t grow on ordinary media – requires cysteine or cystine
for growth
Francisella tulerensis
 Found living in water as an intracellular parasite of animals
 Causes the zoonotic disease tuleremia
 Spread to humans occurs mainly through the bite of an infected
Dermacentor or by contact with an infected animal
 The bacteria can spread through unbroken skin and mucous
membranes, making it highly infectious
 Tuleremia produces symptoms common to other bacterial and viral
diseases and may be misdiagnosed
Francisella
 Entry through skin abrasions (ulceroglandular form of the
disease) - after ~ 48 hours a lesion occurs at the inoculated site.
 Symptoms





Ulcer
Headaches,
Pain and
Fever
Adjacent lymph nodes become enlarged.
 If not contained, this can progress to septicemia, pneumonia, and
abscesses throughout the body.
 The organism survives for long periods of time inside phagocytic cells).
Francisella
 Ingestion (typhoidal form of the disease)
 the focus of infection is the mouth, throat, and GI tract.
 Inhalation (pneumonic form of the disease)
 This is the most severe form of the disease and it manifests as a
pneumonia with a high mortality rate of 30% in untreated cases.
 Antimicrobial susceptibility
 Streptomycin or tetracycline
 An attenuated, live vaccine that protects against the inhalation
form of the disease is available for those exposed to the
organism.
Prevention
 A vaccine is available to at risk individuals
 Preventing infection is done by avoiding the major reservoirs of the
bacteria
Brucella
 Classification
 Are all intracellular organisms
 4 species can infect humans
 B. abortus
 B. suis
 B. melitensis
 B. canis
 Morphology and cultural characteristics
 Small g-cb that stain poorly
Brucella
 Antigenic structure
 2 antigens that are part of the LPS are recognized: A and M
 B. melitensis has the highest concentration of M and causes the most serious
infections
 Virulence factors
 Endotoxin
 Clinical significance
 Has a tropism for erythritol
 Animal fetal tissues and placenta, other than those in humans, are rich in
erythritol and, therefore, the organisms often cause abortions in these
animals.
Brucella
 Causes Brucellosis or undulent fever in man following ingestion
of contaminated milk or cheese from goats (B. melitensis), cows
(B. abortus), pigs (B. suis), or canines (B. canis).
 Man can also acquire the organism via contact with infected animals.
 Clinical manifestations range from subclinical, to chronic with low grade
symptoms of low fever and muscular stiffness, to acute with fever and
chills.
 The fever typically spikes each evening and this coincides with the release
of organisms from phagocytes (hence the name undulent fever).
 The patient may also experience malaise, weakness, enlarged lymph
nodes, weight loss, and arthritis.
Brucella
 Antibiotic susceptibility
 Chemotherapy is difficult because of the intracellular survival of
the organism.
 Tetracycline for 21 days, sometimes combined with
streptomycin.
Pseudomonads
 Gram-negative, aerobic bacilli
 Ubiquitous in soil, decaying organic matter, and almost every moist
environment
 Problematic in hospitals because they can be found in numerous
locations
 Opportunistic pathogens
Pseudomonas aeruginosa
 Rarely part of the normal microbiota
 Opportunistic pathogen of immunocompromised patients
 Can colonize almost every organ and system and result in various
diseases
 Often infects the lungs of cystic fibrosis patients
 The bacteria form a biofilm that protects them from phagocytosis
 Increases the likelihood of death in these patients
Pseudomonas aeruginosa
 Diagnosis can be difficult as the presence of bacteria may
represent contamination of the sample
 Treatment is difficult because P. aeruginosa is resistant to many
antibacterial drugs
Miscellanous Bacterial Pathogens
 Stain pink in a Gram stain but differ from typical Gram-negative
organisms
 Have different morphology, growth habits, or reproductive strategies
 Traditionally discussed separately due to their unique features
Spirochetes
 Thin, tightly coiled, helically shaped bacteria
 Moves in a corkscrew fashion through its environment
 This movement is thought to enable pathogenic spirochetes to burrow
through their hosts’ tissues
 3 genera cause human disease
 Treponema, Borrelia, and Leptospira
Treponema pallidum pallidum
Cannot survive in the environment
Lives naturally only in humans as an obligate parasite
Causative agent of syphilis
Syphilis occurs worldwide
Transmission is almost solely via sexual contact
Endemic among sex workers, men who have sex with men, and
users of illegal drugs
 Can also be spread from an infected mother to her fetus






 Often results in the death of the fetus or in mental retardation and
malformation
Treponema pallidum pallidum
• Syphilis can proceed through four stages
– Primary-symptoms associated with the initial
infection
– Secondary-related to spread of the organisms
away from the site of the original infection
– Latent
– Tertiary syphilis
Primary Syphilis
• Symptoms include:
– Chancre that should heal by
itself in 3-6 weeks
• painless
–
–
–
–
•
129
genitals
Mouth
Skin
rectum
Enlarged lymph nodes near
the chancre the chancre
Secondary Syphilis
 Spotted rash all over
 Fever
 general ill feeling
 loss of appetite
 muscle aches
 joint pain
 enlarged lymph nodes
 hair loss may occur.
130
Tertiary Syphilis
 Cardiovascular syphilis
causes aneurysms or valve
disease
 Central nervous system
disorders (neurosyphilis)
 Infiltrative tumors of skin,
bones, or liver (gumma)
131
Diagnosis, Treatment, and Prevention
 Diagnosis
 Primary, secondary, and congenital can be readily diagnosed with
antibody tests against bacterial antigens
 Tertiary syphilis is difficult to diagnose
 Treatment
 Penicillin is the drug of choice except with tertiary syphilis which is a
hyperimmune response and not an active infection
 Prevention
 Abstinence and safe sex are the primary ways to avoid contracting
syphilis
Borrelia
• Lightly staining, Gram-negative spirochetes
• Cause two diseases in humans
– Lyme disease
– Relapsing fever
Lyme Disease
 Borrelia burgdorferi is the causative agent
 Bacteria are transmitted to humans via a tick bite
 Hard ticks of the genus Ixodes are the vectors of Lyme disease
135
Lyme Disease Pathology
 Shows a broad range of signs and symptoms
 3 phases of disease in untreated patients
 In most cases an expanding red “bull’s eye” rash occurs at the site of
infection
 Neurological symptoms and cardiac dysfunction
 Severe arthritis that can last for years
 Pathology of this stage is largely a result of the body’s immune response
Lyme Disease Pathology
 The increase of cases is a result of humans coming in closer
association with ticks infected with Borrelia
 Antimicrobial drugs can effectively treat the first stage of Lyme
disease
 Treatment of later stages is difficult because symptoms result from
the immune response rather than the presence of bacteria
 Prevention is best achieved by taking precautions to avoid ticks
Relapsing Fever
 2 types of relapsing fever
 Epidemic relapsing fever
 Endemic relapsing fever
Epidemic Relapsing Fever
 Mortality rate is 1% with
treatment; 30-70% without
treatment
 Transmitted by lice
Mortality rate is
1% with treatment;
30-70% without
treatment
Endemic Relapsing Fever
 Several Borrelia species can cause this
disease
 Transmitted to humans by soft ticks of the
genus Ornithodoros
Relapsing Fever
 Both types of relapsing fever are
characterized by recurring episodes of fever
and septicemia separated by symptom free
intervals
 Pattern results from the body’s repeated efforts
to remove the spirochetes,which continually
change their antigenic surface components
Relapsing Fever
 Observation of the spirochetes is the primary method of
diagnosis
 Successful treatment is with antimicrobial drugs
 Prevention involves avoidance of ticks and lice, good
personal hygiene, and use of repellent chemicals
142
Mycoplasmas
 Smallest free-living microbes
 Lack cytochromes, enzymes of the Krebs cycle, and cell walls
 Often have sterols in their cytoplasmic membranes which other
prokaryotes lack
 Require various growth factors that must be acquired from a host or
supplied in laboratory media
 Can colonize the mucous membranes of the respiratory and urinary
tracts
Mycoplasma pneumoniae
 Attaches specifically to receptors located at the bases of cilia on
epithelial cells lining the respiratory tracts of humans
 Causes primary atypical pneumonia, or walking pneumonia
 Symptoms such as fever, headache, and sore throat are not typical of
other types of pneumonia
 Not usually severe enough to require hospitalization or to cause death
 Spread by nasal secretions among people in close contact
Mycoplasma pneumoniae
 Diagnosis is difficult because mycoplasmas are small and grow
slowly
 Prevention can be difficult because patients can be infective for
long periods of time without signs or symptoms
Rickettsias
 Extremely small (not much bigger than a smallpox virus)
 Appear almost wall-less due to the small amount of peptidoglycan
present
 Obligate intracellular parasites
 Unusual because they have functional genes for protein synthesis,
ATP production, and reproduction
 Three genera cause disease in humans
 Rickettsia, Orienta, and Ehrlichia
Characteristics of Rickettsias
Table 21.1
Rocky Mountain Spotted Fever
 Symptoms usually develop about 2 to 14 days after the tick bite. They may











148
include:
Chills & Fever
Severe headache
Muscle pain
Mental confusion & Hallucinations
Rash
Abnormal sensitivity to light
Diarrhea
Excessive thirst
Loss of appetite
Nausea &Vomiting
Spread by ticks
Endemic Typhus
 Chills
 Cough
 Delirium
 High fever (104 degrees Fahrenheit)
 Joint pain (arthralgia)
 Light may hurt the eyes
 Low blood pressure
 Rash that begins on the chest and spreads to the rest of the body (except the
palms of the hands and soles of the feet)
 Severe headache
 Severe muscle pain Stupor
 Spread by fleas
149
Epidemic Typhus
 Abdominal pain
Spread by lice
 Backache
 Dull red rash that begins on the middle of the body and spreads
 Extremely high fever (105 - 106 degrees Fahrenheit), which may





150
last up to 2 weeks
Hacking, dry cough
Headache
Joint pain (arthralgia)
Nausea
Vomiting
Chlamydias
 Do not have cell walls
 Have two membranes but without any peptidoglycan between them
 Grow and multiply only within the vesicles of host cells
 Have a unique developmental cycle involving two forms
 Both forms can occur within the phagosome of a host cell
Chlamydia trachomatis
 Has a limited host range
 One strain infects mice, all others infect humans
 Infect the conjunctiva, lungs, urinary tract, or genital tract
 Enters the body through abrasions and lacerations
 Clinical manifestations result from the destruction of infected cells
at the infection site, and from the resulting inflammatory response
Chlamydia trachomatis
 Causes two main types of disease
 Sexually transmitted diseases
 Causes the most common sexually transmitted disease in the United States
 Ocular disease called trachoma
 Occur particularly in children
 Endemic in crowded, poor communities with poor hygiene, inadequate sanitation,
and inferior medical care
Chlamydia—Rates by Sex, United States, 1990–2009
Rate (per 100,000 population)
600
Men
Women
Total
500
400
300
200
100
0
1990
1992
1994
1996
1998
2000
2002
2004
Year
NOTE: As of January 2000, all 50 states and the District of Columbia had regulations that required chlamydia cases to be
reported.
2006
2008
Sexually Transmitted Diseases
 Lymphogranuloma veneruem
 Characterized by a transient genital lesion and swollen, painfully
inflamed, inguinal lymph nodes
 Occurs in three stages
 Initial stage
 Produces a lesion at the infection site that is small painless, and heals rapidly
 Second stage
 Buboes develop at the infection site
Sexually Transmitted Diseases
 Third stage
 Only some cases progress to this stage
 Characterized by genital sores, constriction of the urethra, and genital
elephantiasis
 Most infections in women are symptomatic but men may or may not
have symptoms
 Women can develop pelvic inflammatory disease if reinfected with
C. trachomatis
Trachoma
 Disease of the eye
 Leading cause of nontraumatic blindness in humans
 Bacteria multiply in the conjunctival cells resulting in scarring
 The scarring causes the eyelashes to turn inwards and abrade the
eye that can eventually result in blindness
Trachoma
 Typically a disease of children who have been infected during birth
 Infection of the eye with bacteria from the genitalia can also result
in disease
Diagnosis, Treatment, and Prevention
 Diagnosis
 Demonstration of the bacteria inside cells from the site of infection
 Treatment
 Antibiotics can be administered for genital and ocular infections
 Surgical correction of eyelid deformities from Trachoma may prevent
blindness
Diagnosis, Treatment, and Prevention
 Prevention
 Abstinence and safe sex can prevent sexually transmitted chlamydial
infection
 Blindness can only be prevented by prompt treatment with
antibacterial agents and preventing reinfections
Legionella pneumophila
 Aerobic, slender, pleomorphic bacteria
 Universal inhabitants of water
 Humans acquire the disease by inhaling the bacteria in aerosols
from various water sources
 Intracellular parasites
Legionella pneumophila
 Causes Legionnaires’ disease
 Results in pneumonia
 Immunocompromised individuals are more susceptible
 Elimination of the bacteria is not feasible but reducing their number
is a successful control measure
Bartonella
 Gram-negative aerobic bacilli
 Found in animals but only cause disease in humans
 3 species are pathogenic
 Bartonella bacilliformis
 Bartonella quintana
 Bartonella henselae
Bartonella bacilliformis
Bartonellosis -Carrión’s Disease
Transmitted by blooding-sucking sand flies
• Acute phase: (Carrion's disease)
• fever
• pallor, malaise,
• nonpainful hepatomegaly,
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jaundice,
lymphadenopathy,
splenomegaly.
This phase is characterized by severe hemolytic
anemia and transient immunosuppression.
The case fatality ratios of untreated patients
exceeded 40% but reach around 90% when
opportunistic infection with Salmonella occurs.
Bartonella quintana
 Trench fever
 Spread person to person by human body lice
 Also causes disease in immunocompromised patients
 The disease is classically a five-day fever of the relapsing
type
Bartonella henselae
 Cat scratch fever
 Introduced into humans through cat scratches or bites
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