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: Location: Non-inflammatory

(enterotoxin) proximal small bowel

Illness: Stool exam: Diarrhea

no fecal leukocytes

Example organisms:

V. cholerae

E. coli Salmonella

Campylobacter Giardia Cryptosporidium

Rotavirus Norwalk-like agents

II Inflammatory

(invasive, cytotoxin) colon

III Penetrating

(invasive, spread) distal small bowel

Dysentery

blood, fecal PMNs (polymorphonuclear leukocytes = neutrophils)

Shigella

Invasive E. coli

S. enteritidis

C. difficile E. histolytica B. coli

Enteric fever

fecal mononuclear leukocytes (monocytes, lymphocytes)

S. typhi Y. enterocolitica

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)

vegetation, normal intestinal flora ~40 genera, 150 species soil, water,

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

www.mc.maricopa.edu MacConkey agar selective and differential 16 http://class.fst.ohio-state.edu

Green sheen; black nucleated centers EMB agar selective and differential

TSI

Yellow = sugar fermentation Black = H 2 S positive Air bubble = gas production 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), H 2 S production (black) Note: Shigella is a non-fermenter, H 2 S K. pneumoniae (L); M. luteus (R) S. typhimurium (L); P. vulgaris (R) H 2 S 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 (S Mac)

 most

E. coli

can ferment sorbitol (form pink colonies) 

E. coli

O157:H7

does not ferment sorbitol

are clear/colorless) (colonies

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

the USA) (except EHEC is common in  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

effect seems to have a strong protective  IgA and other factors decrease bacterial attachment 25

Enterotoxigenic

E. coli

“Traveler’s diarrhea”

(ETEC)     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 ~60 deaths   estimated that only

~100 cells

infection can cause 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

    hemolytic anemia thrombocytopenia kidney failure 5-10% of kids infected with EHEC

(HUS)

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: 10 8 -10 10   

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, H 2 S 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. c

holeraesuis

, serovar

typhi

  often just called:

S. typhi

Better designation:

Salmonella Typhi

S. enterica

ssp. e

nterica

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, C 1 , C 2 , D, and E) based on O-antigen antisera 37

 

Salmonella

infection

 human intestinal disease due to

ingestion

bacteria (contaminated food/water) of 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 infections

typhoid

Salmonella

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

(~10 3 versus 10 6 -10 infections with other species of

Salmonella)

8 for    

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

43

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.

www.pbs.org

 

Diagnosis and treatment of typhoid fever

 

culture

blood of

S.

Typhi

/S.

Paratyphi from patient  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)   H 2 S 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

humans transmission from infected 

highly communicable

produce disease) (need only ~200 cells to  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 cells cause “ruffling” of epithelial  allows for endocytosis of the bacteria  actin rearrangement allows for cell-to-cell spread 

S. dysenteriae

EHEC) produces

shiga toxin

(similar to 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 Yersinia

sp.

more common than other enteric 

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 Enterotoxin

V. cholera

ETEC

K. pneumoniae

8-72h 2-4+ 1-2+ 0-1+ 58 Enteroadherent EPEC EAEC

Giardia Cryptosporidium

Helminths

1-8d 0-1+ 1-3+ 0-1+

Harrison’s principles of internal medicine, 2005

3-4+, watery 3-4+, watery

Diarrhea pathobiology, #2

Agent Incubation period Vomiting Abdominal pain Fever Cytotoxin producers

C. difficile

1-3d

EHEC

12-72h 0-1+ 3-4+ 1-2+

Diarrhea

1-3+, usually watery, occasional bloody 1-3+, initially watery, quickly bloody

59

Diarrhea pathobiology, #3

Agent Invasive

minimal inflammation Rotavirus Norwalk agent moderate inflammation

Salmonella

Camylobacter V. parahaemolyticus

Yersinia

severe inflammation

Shigella

EIEC

E. histolytica

60 Incubation period

1-3d 12h-11d 12h-8d

Vomiting

1-2+ 0-3+ 0-1+

Abdominal pain

2-3+

Fever

3-4+ 2-4+ 3-4+ 3-4+

Diarrhea

1-3+, watery 3-4+ 1-4+, watery or bloody 1-2+, bloody

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% CO 2

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 Guam 58.1 67.3

40.1

14.4

93.4

115.6

36.0

94.9

100.2

20.7

69.4

23.6

79.2

89.9

24.0

47.3

81.5

80.5

139.5

64.4

125.1

90.7

154.9

66.3

175.9

158.2 139.2

167.4

52.5

78.5

92.2

85.6

199.4

162.6

154.9

242.5

10.4

VT 11.6

NH 13.7

MA 38.0

RI 47.2

CT 74.4

NJ 63.0

DE 176.0

MD 130.8

DC 342.8

Rate per 100,000 population 257.1

234.0

216.8

<=19.0

133.2

240.6

134.8

19.1-100.0

>100 (n= 5) (n= 27) (n= 22) Puerto Rico 7.7 Virgin Is. 31.3 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.

Men 750 600 450 300 150 Rate (per 100,000 population) 0 Age 0 150 300 450 Women 600 750 6.3

279.1

454.1

320.9

185.7

130.8

93.5

53.0

18.4

4.2

117.1

10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-54 55-64 65+ Total 35.1

65.7

125.5

33.9

12.9

2.9

0.7

124.6

294.9

647.9

605.7

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

93

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

94

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.

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

96

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)

97

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

98

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

less likely to benefit from treatment.  The treatment does not work in all patients.

are Treatment must be taken for 10 to 14 days. Medications may include: Two different antibiotics Proton-pump inhibitor, Bismuth subsalicylate (Pepto-Bismol)

Haemophilus

   Small, pleomorphic bacilli Obligate parasites due to their requirement of heme and NAD + growth for 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

104

Stages

   Catarrhal Paroxymal Convalescence

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 hypoglycemia such as increased insulin release and the resulting 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

–

B. bronchoseptica

  causes a mild form of whooping cough 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 – for growth requires cysteine or cystine

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. melitensis B. canis

Morphology and cultural characteristics 

B. abortus B. suis

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

129 • •

Primary Syphilis

Symptoms include: – Chancre that should heal by itself in 3-6 weeks • painless – genitals – – – Mouth Skin rectum Enlarged lymph nodes near the chancre the chancre

130        

Secondary Syphilis

Spotted rash all over Fever general ill feeling loss of appetite muscle aches joint pain enlarged lymph nodes hair loss may occur.

131

Tertiary Syphilis

 Cardiovascular syphilis causes aneurysms or valve disease  Central nervous system disorders (neurosyphilis)  Infiltrative tumors of skin, bones, or liver (gumma)

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

142

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

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

148            

Rocky Mountain Spotted Fever

Symptoms usually develop about 2 to 14 days after the tick bite. They may 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

149

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

150

Epidemic Typhus

         Abdominal pain Nausea Vomiting 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 last up to 2 weeks Hacking, dry cough Headache Joint pain (arthralgia)

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) 600 500 Men Women Total 400 300 200 100 0 1990 1992 1994 1996 1998 2000 Year 2002 2004 2006 2008

NOTE:

As of January 2000, all 50 states and the District of Columbia had regulations that required chlamydia cases to be reported.

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, 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. 164

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

166

Bartonella henselae

  Cat scratch fever Introduced into humans through cat scratches or bites