Part 17-3. Infectious Diseases

Chapter 181. Pertussis

Etiology

# ★Bordetella pertussis

    ; *sole cause of epidemic pertussis & usual cause of sporadic pertussis

# B. parapertussis

    ; occasional cause of pertussis

  ; 미국에서는 Bordetella species의 5% 이하

# B. pertussis, B. parapertussis - exclusive pathogens of humans

  4. B. bronchiseptica

    ① a common animal pathogen, occasional case reports in human

    ② immunocompromised patient or young children with unusual exposure to animal

  5. protracted cough

     : caused by Mycoplasma, parainfluenza or influenza viruses, enterovirues, RSV,

       or adenovirus

Epidemiology

  1. wide spread use of pertussis vaccine : dramatic decline in cases

  2. vaccine coverage가 낮은 Italy & Germany의 어떤지역, less potent vaccine을 사용하는 Nova Scotia에서

     ds에 대한 high incidence와 immunization중단후 질환의 dramatic한 재발은 vaccine의 중요한 역활를 증명       한다.

  3. endemic with superimposed epidemic cycles every 3 ∼ 4 yr

  4. case의 대부분은 7월에서 10월 사이 발생

  5. 매우 전염성이 강해 close range내 aerosol droplets노출시 susceptible individual에서는 100%의 attack rate

  6. household처럼 intense expose시, subclinical inf의 rate는 immunized & naturally immune individual에서

     ---> 50%

  7    natural disease나 vaccination은 ds나 reinfection에 대해

       → complete 혹은 lifelong immunity 제공하지 못함

       typical ds.에 대한 protection은 vaccination후 3 ∼ 5yr내 감소가 시작해 12yr후는 측정안됨

  8. ds나 complete immunization의 hx에도 불구하고 pertusis  발생되는 경우

        in the eldely

        in nursing homes

        in residential facilities with limited exposure

        in highly immunized suburbia

        in adolescent & adults with lapsing time since immunization

  9. coughing adolescent & adults

        major reservoir for B. pertusis currently

        the usual sources for  " index case " in infants & children

  10. prevaccine era 나 Germany, Sweden, Italy 같은 limited immunization지역에서          

      pertussis의 peak incidence : 1 ∼ 5 yr

     → 1세 이하의 infants에서는  case의 15%이하

  11. 1993년동안 미국에서 보고된 pertussis 5000 cases

        44 % : 1세 이하

        21 % : 1 ∼ 4 세

        11 % : 5 ∼ 9 세

        24 % : 12 세이상

        1 세이하에서 79%는 6개월 이하였고 immunization의 잇점이 거의 없는 상태다

  12. 7개월에서 4세 사이의 pertussis children : underimmunized

  13. teenages와 adults에서 pertussis비율은 현재증가되는데

      → 1992-1993 년사이 27 %

         prevaccine area에서는 20%이하

  14. B. pertussis 의 natural reinfection혹은 repeated booster vaccination없이

      → old children과 adults는 expose된다면 clinical ds 가 발생할 수 있고

         mother는 young infant에 passive protection이 있다하더라도 거의 없다

Pathogen & Pathophysiology

1. Bordetella

       tiny gram-negative cocobacilli

       grow aerobically on

       : starch blood agar or completely synthetic media with nicotinamide growth factors,

        amine acid for energy, charcoal or cyclodexintrin resin to absorb noxious substance

2. B. pertussis (only)

   :  pertussis toxin (PT)

      - major virulence protein

3. Serotyping

        heat- labile K agglutinogen에 좌우

        14 agglutinogen중 6번은 B. pertussis에 specific      

4. B. pertusisa는 ds와 immunity에 역활을 하는 active substance를 생산

  ; aerosol acquisition 후

 → filamentous hemaggllutinin ( FHA )

    some agglutinogens ( esp, FIM2 & FIM3 )

    69-KD nonfimbrial surface protein ( called pertactin (PRN))

 → ciliated respiratory epithelial cell의 attachement에 중요

5. Tracheal cytotoxin, adenylated cyclase, PT

 → inhibit clearance of organisms

6. Tracheal cytoxin, dermonecrotic factor, adenylate cyclase

     local epithelial cyclase

     produce respiratory symptomatology

     facilitates absorbtion of PT

7. PT

     multiple proven biologic activities를 가짐

    : histamine sensitivity, insulin secretion, leukocyte dysfunction

     ds의 systemic manifestation의 이유

     experimental animal 에서는 lymphocytosis 야기

     pathogenesis에서는 중심적인 역활

Clinical Manifestation

1. pertussis : lengthy ds

    catarrhal           .  -+       

    paroxysmal            |   each lasting 2 wk   

    convalescent stages   -+       

2. incubation period (3 ∼ 12 days) 후

   → congestion & rhinorrhea의 nondistinctive catarrhal sx 발생

   → low grade fever, sneezing, lacrimation, conjuntival suffusion 동반

3. 증상감소후 dry, intermittent, irritative hack형태로 cough가 처음 시작

   → pertussis hallmark인 inexorable paroxysms으로 발전

4. drought, light, sound, sucking, or stretching로 부터의 insignificant startle후 choke,

   gasp, flail extremities, eye watering, & bulging, face reddened 보임

   : 이stage에서 cough (-) 수도

5. whoop (forceful inspiratory gasp)

     infrequently occurs in infants under 3 mo.

     exhausted

     lake muscular strength to create

     sudden negative intrathoacic pressure

6. insignificant provacation있는 well- appearing playful toddler는 잠자는 anxious aura

   나타남

   → chin & chest 는 forward 유지하며, tongue는 protruding maximally,

     eye bulging,& watering, face purple, (last moment of consciousness까지)

   → cough 중단, 부분적으로 closed된 airway를 inspirated air가 지날때 loud whoop (+)

     : 이러한 episode는 inspissated tracheal secretion, denude cilia, necrotic epithelium 

       의 thick plug를 expulsion후  끝남

7. post-tussive emesis

      common in pertussis at all ages

      major clue to the diagnosis in adoesents & adults

8. the number & severity of paroxysms

      며칠에 걸쳐 week (more rapiddly in young infants)

      며칠 혹은 몇 주에 걸처 plateau 지속될 수도 (longer in young infants)

9. at the peak of paroxysmal stage

   : 매 시간마다 하나이상의 episode(+)

10. paroxysmal stage가 convalesence로 진행되면서

   : episode의 numbers, severity, duration감소

11. immunized children

   : foreshortening of all stages of pertussis

12. adult

    : no distinct stages

13. infants under 3 mo

    catarrhal phase : usually a few days

    apnea, chocking, gasping, cough가 ds의 onset을 알릴때 모두에게서

    catarral phase가 인지되는 않는다 

14. convalescence

    : intermittent paroxysmal coughing thought the 1st yr of life

      → including recurrence with subsequent respiratory illness

15. phy/exam: generally uninformative

   sign of lower respiratory tract ds: not expected

   conjuntival hemorrhges & petechiae on the upper body: common

Diagniosis & Differential Diagnosis

1. pertussis suspected

  : pure or predominent complaint of cough

   (특히 fever, malaise, myalgia, exanthem or enathem, sore throat, hoarseness,

     tachypnea, wheezes, rales 없는 경우)

2. sporadic case 에서

    paroxysms, whoop, post-tussive vomitng 중 한가지 이상과 함께

    14일 이상의 cough에 대한 clinical case definition은,

    culture confirmation에 대해 81%의 sensitivity, 58%의 specificity

3. apnea or cyanosis (before appreciation of cough): clue in infants unders 3 mo

4. B. pertusis

   : occasional cause of suuden infant death

5. Adenoviral inf

   : fever, sore throat, conjunctivits와 같은 동반 증상으로 보통 구별

6. Mycoplasma

      protracted episodic coughing

      hx of fever, headache, & systemic sx at the onset of disease

      frequently finding of rale on ausculation of the chest

7. B. pertussis

   : associated uncommonly with

      sataccato cough ( breath with every cough )

      purulent conjunctivitis

      tachypnea

      rales or wheezes ( chlamydia, trachomatis inf의 특징임 )

      predominent lower respiratory tract signs ( RSV inf의 특징임 )

8. pertussis infant에서 2차적인 bacterial pn(-) 인 경우

   : paroxysms 사이  exam에서 전반적으로 normal

     (respiratory rate 포함해서)

9. leukocytosis (15,000 ∼ 100,000 cells/mm³)

   due to absolute lymphocytotosis

      characteristic late catarrhal & paroxysmal stage

      lymphocyte: T & B - cell origin normal small cells

      adults & partially immune children: less impressive lymphocytosis

10. absolute increase in neurophils: a different diagnosis & secondary bacterial inf.

 

11. eosinophilia: not common in pertussis even in youg infant

12. severe course & death : correlated with extreme leukocytosis

    (mean peak WBC count fatal vs nonfatal cases, 94 & 18 × 10⁹ cells/L)

        thrombocytosis (meam peak platelet count fatal vs nonfatal cases, 782 vs 556 × 10⁹ cells/L)

13. mild hyperinsulinemia & reduced glycemic response to epinephrine

     : demonstrated

14. hypogycemia : occasionally

15. the chest radiography

      mildly abnormal in the majority of hospitalized infant

     → showing perihilar infiltrate or edema (때때로 butterfly appearance)

      parenchymal consolidation

     : suggest secondary bacterial infection

      pneumothrax, pneumomediasinum, air in soft tissues

     : occasionally

16. isolation of B. pertussis in culture

   the gold standard & more sensitive & specific method of Dx than direct fluoresent  

   antibody (DFA) testing of nasopharyngeal secretion (careful attention 주어진다면)

17. culture

     positive during the catarrhal stage & escalating paroxysmal stage

     less positive in partially immune individual & amoxillin, erythromycin 투여받은 환아

     specimen

     : obtained by deep nasopharyngeal aspiration or by use of a flexible swab

      (Dacron or calcium algimate preferred) in the posterior nasopharyngeal

      for 15∼30sec (or until coughing)

     Stainer-Schotle broth or Regan-Lowe semisolid tranport media

     : used for longer periods, up to 4 days

     Regan-Lowe charcoal agar with 10% horse blood & 5∼40㎍/㎖ cephaloxin or       

     Stainer-Scholte media with cyclodestrine resin

     incubated at 35 ∼ 37 ℉ in humid envionment & examine daily for 7 days for

     slow-growing, tiny glistening colonies

18. Direct testing of nasopharyngeal secretios by DFA

     rapid test, eap helpfu in patients who received antibiotics

     only reliable in laboratoreis with continuous experience

19. serologic tests for dection of a variety of Ab to components of the organism

    in acute & convalescent sample

      the most sensitive tests, useful epidemiologically

      not generally available, not helpful during acute illness

      difficult to interpret in immunized in dividuals

Complications & Prognosis

1. infants under 6 mo of  age

   : excessive mortality & morbidity

2. under 2 mo of age

   : highest reported rates of pertussis-associated hospitalization (82%)

        Pneumonia(25%), seizure (4%) , encephalopathy(1%)  death (1%)

 

3. the principal complications of pertussis

   : apnea, secondary inf. (such as otitis media & pn)

     physical sequale of forceful coughing

4. apnea, cyanosis & secondary bacterial pn

   : events precipitating intubation & ventilation

5. bactrial pneumonia &/or ARDS

   the usual cause of death at any age

6. pulmonary hemmrrhage

   : occured in the neonate

7. fever, tachypnea or respiratory distress between paroxysms & absolute neutrophilia

      clue to pneumonia

       espected pathogen

      : staph. aureus, s. pneumoniae, bacteria of mouth flora

8. Bronchiectasis : rare

9. abnormal pulmonary function               

    : persist for 12 mo after uncomplicated pertussis in children under 2 yr

10. increased intrathoracic & intra-abnormal pressure during cough result

      conjuntival & scleral hemorrhages

       petechiae on the upper body

       epistaxis

       hemorrhage in the CNS & retina

       pneumothrax & subcutaneous emphysema

       unilateral & inguinal hernia

11. laceration of the lingual frenulum : common

    rectal prolapse : frequent reported

     → due to pertussis in malnourished children or missed diagnosis of cytic fibrosis

12. infants in developing countries

    dehydration & malnutrion following post-tussive voming

13. tetany: assiciated with profound post-tussive alkalosis

 

14. CNS abnormalities      

       relatively high frequency

       always the result of hypoxemia or hemorrhage associated with coughing or apnea 

      in young infants

15. apnea or bradycardia or both

       from apparent laryngospasm or vagal stimulation just before a coughing episode

       from obstruction during an episode

       from hypoxemia following an episode

16. lack of associated sign in some young infants with apnea

    : ↑ possibility of a primary effect of PT on CNS

17. seizure

    : usually result of hypoxemia

      hyponatremia from SIADH during pneumonia

Treatment

Assessment And Supportive Care

1. goals of therapy

       limit the number of paroxysms

       observe severity of cough to provide assistance when necessary

       maximize nutrition

       rest & recovery without sequelae

2. high risk for severe disease

       prematurely born young infants

      children with underlying cardiac, pulmonary, muscular or neurologic disorders

3. the specific, limited goals of hospitalization

     assess progression of disease & likehood of life-threatening events at peak of ds

       prevent or treat complications

       educate parents in the natural history of disease & in care that will be given

      at home

4. life threatening 하지 않는 typical paroxysm의 following feaures

       duration less than 45 sec

       red but not blue color change

       tachycardia, bradycardia ( not < 60 beats/min in infants )

       oxygen desaturation- paroxysm 끝에 resolve

       whooping or strength for self-rescue at the end of the paroxysm

       self-expectorated mucus plug

      post-tussive exhaustion but not unresponsiveness

5. Mist by tent

    : useful in some infants with thick tenacious secretion & excessively irritable

6. feeding

       the risk of precipitating cough by nipple feeding

      : most infans에서 nasogastric, nasojejunal, or parenteral alimentation의 근거는 아니다

       formula의 composition 혹은 thickness

      : secretion의 quality, cough retension에 영향을 주지않는다

       large-volume : avoided

7. Apnea, & seizure

    : occur in the incremental phase of illness & in complicated ds

Therapeutic Agents

Antimicrobial Agents

    ; *EM 40-50 mg/Kg/24hr, orally in four divided dose (maximum 2g/24hr ) for 14 days

           - standard Tx

    ; EM ethylsuccinate

       : 50 mg/Kg/24hr. divided into two doses

        60 mg/Kg/24hr. divided into three doses

  ; EM estolate

      : 40 mg/Kg/24hr divided into two doses

        - children의 98%에서organism 제거

       Ampicillin, rifampin, trimethoprim-sulfamethoxazole

      :  moderately active

          1st & 2nd generation cephalosporins : not active

       in clinial studies

      EM : superior to amoxillin for eradication of B. pertussis

               only agent with proven efficacy

Salbutamol

   : modest reduction of sx from the β2-adrenergic stimulant salbutamol

Corticosteroids

Pertussis Immune Globulin

    ; *not warranted

Control Measure

Isolation

    ; at least 5 days after initiation of EM therapy

Care Of Household & Other Close Contacts

    ; *all houshold contacts & other close contacts regardless of age, hx of immunization, or symptomatology

           - EM 40-50 mg/kg/24hr orally in four divided doses (maximum 2g/24hr ) for 14 days

    ; visitation & movement of coughing family members in the hospital

           - controlled untill taken EM *for 5days

    ; *close contacts younger than 7yr, underimmunized

           - *pertusis-containg vaccine

    ; children younger than 7 yr received a 3rd dose 6mo or more before exposure or 4th dose 3yr or more before exposure

           - booster dose

Prevention

    universal immunization of children with pertusis vaccine beginning in the infancy

   - central to control of pertusis

Whole Cell Vaccine

    ; 미국에서 primary immunization과 세계 대부분지역에서 사용하기 위해 WHO에 recommand된 vaccine

      : killed whole cell vaccine

         composed of asuspension of inactivated B. pertusis,

        combined with diphtheria & tetanus (DT) toxoids & aluminum-containing adjuvants (DTP vaccine)

       vaccine potency

       a. opacity unit (also a safety standard) or protective units

      b. U.S. preparations

         : 4 ∼ 12 protective unit & nor more than 16 opacity units per 0.5 ml/dose

# ★Efficacy Of Whole Cell Vaccine

  ; 64% for mild cough

  ; 81% for paroxysmal cough

  ; 95% for severe clinical illness

       individuals over 7 yr of age

      : not routinely given pertussis-containing vaccine

       a major limitation of whole cell vaccine : reactogenecity

       DT와 비교해서 DTP vaccien 에서는 significantly more local reactions

       : fever, fretfulness, crying, drowsiness & vomiting

        → immunization 수시간 발생하여 sequelae없이 spotaneous subside

       DTP vaccine 후

       : anaphylaxis 혹은 sterile abscess → extremely rare

       Transient urticaria : uncommon, related to circulating antigen antibody complex

       seizure

          occuring within 48 hr of approximimately 1 : 1750 doses administered

          brief, generalized, & self-limited

          occuring in feberile children in almost all instance

          more commonly

          : personal or Fhx of convulsion

            not result in epilepsy or permanent neurologic sequelae

       persistent inconsolable crying  or screaming for 3 or more hours

       : reported after  1% of doses administered

         manifestation of pain in many instances

   ⑩ collase or shock like state (hypotonic-hyporesponsive episode)

       : observed after approximately 1 : 1750 pertussis vaccination,

        usually in young infants

   ⑩① severe adverse events

        : death, encephalopathy, onset of a seizure disorder, developmental delay

         learning or behaiviorol problems

          → occured in individuals temporally associated with pertussis immunization

            or alleged to be causally associated               

Acelluar Vaccine

    ; purified component acellular pertusis (aP) vaccines

    ; originally developed in Japan

    ; *licensure for use in children 15mo of age or older as the 4th and/or 5th doses

Chapter 182. Salmonellosis

Etiology

1. salmonella

       belong to the family enterobactriaceae

       three species : S. typhi, S. choleraesuis, S. enteritidis

       motile, nonsporulating, non capsulated, gram-negative rods

2. Most strains

       glucose, mannose, mannitol 발효 (+)

       lactose, or sucrose 발효 (-)

3. salmonellosis는 많은 physical agents에 resistant하지만

   → 130℉ ( 54.4℃ ) for 1hr,  140 ℉ ( 60℃ ) for 15min heating으로 killed

4. somatic O antigen

    : heat-sterile lipopolysaccharide component of cell wall

  H antigens

    : heat - labile protein

    : present in phase 1 or 2

5. the Kauffmann-White sheme commonly used to cassify salmonellae serotype

    : based on O & H antigen

6. virulence (Vi) capsular polysaccharide

    : present on S. typi

    : rarely found on strains of S. paratyphi C ( S. hirschfeldii )

182.1 Nontyphoidal Salmonellosis

Epidemiology

1. U.S.에서 매년보고되는 culture-proven salmonellosis의50,000 중

    98%는 nontyphoidal salmonellosis       

2. reported case

       1/2 : 20 yr↓

      1/3 : 40 yr↓

       highest isolatioin rate : 1yr ↓ infants

3. salmonella infection

    : 미국에서 warm month인 7월 ∼ 11 월 사이에 highest frequency로 발생

4. major reservoir of nontyphoidal salmonellae

    : infected animals

      infected animals → often asx

5. poultry & poultry products ( mainly egg )

    : about half of the common -source outbreaks

6. salmonella inf in chickens

    : ↑ the risk for contamination of eggs

   salmonellae : contaminate the shell penetrate the egg, transmitted from an ovarian infection directly to                     the egg yolk

7. salmonella serotype : isolate

    poultry 의 50 %

    pork의 16 %

    beef 의 5 %

   forzen egg product의 40 %

<신>8. healthy adult에서 symtomatic ds야기위해 ingested되어야하는 bacteria의 수

    : 10⁶ ∼ 10^{8 .}samonella organism

<신>9. high infecting dose때문에 direct fecal-oral spread에 의한 person-to-person 

       transmissiion 은 unusual,

       그러나 toilet - train이 안되는, proper hygiene이 유지안되는 young children에서

       일어날수 있다

10. nonsocomial infection

       related to contaminated medical instruments (특히 endoscope) & diagnostic or pharmacologic

      preparations, 특히 animal origin (e.g. pancreatic extracts, pituiary  extracts, bile salts, pepsin, gelatin,

       vitamins,carmine dye)

       food borne nosocomial tranmissions : also possible

       platelet transfusion에 의한 IV transmission : reported

<신>11. infection 후 nontyphoidal salmonellae

    : excreted in feces for a median of 5 wk 

      in young children & individuals with symtomatic infection → excreted period longer

12. salmonella excretion 기간동안, individual은 다른사람들에게 fecal-oral route

    혹은 contaminating foods에 의해 infection

Pathology

1. enterocolitis

       typical disorder caused by nontyphoidal salmonella infection

       finding : diffuse mucosal inflammation & edema

               때때로 erosion과 microabscesses

2. intestinal inflammation with polumorphonuclear leukocytes & macrophages

    → involves the lamina propria

3. underlying intestinal lymphoid tissue & mesenteric LN

    : enlarge & develop small areas of necrosis

4. hyperplasia of the reticuloendothelial system

    : within liver & spleen

Pthogenesis

# development of disease depends on

    ; the number of infecting organisms

`  ; their virulence traits

    ; several host defense factors

# stomach acidity

    ; *the first protective barrier against ingested samonella organism

    ; inhibits multiplication of the salmonellae

    ; *gastric pH 2.0

           - most organism are rapidly killed

♥Table 182-1 Conditions That Increase The Risk Of Salmonella Bacteremia During Salmonella Gastroenteritis

5. small & large intestine에서 salmonella는 증식과 ds 야기 위해 normal bacterial flora와 경쟁

6. lumen에서 multiplication 후 organism은 ileum의 distal part와 colon의 praximal part의

   mucosa를 penetrate , Peyer path에서 subsequent localization

<신>7. heat-labile, cholera-like enterotoxin과 PG 은 local하게 cyclic adenosine monophosphate level 을

     intestinal crypts 내에서 증가시켜 intestinal lumen으로 electrolyte와 water의 net efflux 를 야기한다

8. 대부분의 diarrhea-associated nontyphoidal salmonelloes와 함께 infection은 lamina propria와

   local lymphatics 아래로 extend되지 않는다.

9. S. dublin & S. choleraesuis

    : rapidly invade the blood stream with little or no intesinal involement

10. bcareremia는 이론적으로 모든 salmonella strain에서 가능한데 특히 reduced host defense 있는 개인에서

       impaired reticuloendothelial or cellular immune response가 중요

      chronic granulomatous ds, other white cell disorders, AIDS 가진 children

       : prone to salmonella septicemia & osteomyelitis

       G-I tract, bone, reticuloendothelial system에서 많은 infarcted areas는 초기에 organism을

      intestine으로 부터 circulation에 대한 적절한 환경을 제공한다.

11. chronic infection은 cholelithiasis, schistosoma mansoni hepatosplenic imvolvement,

   urinary tract schistosoma hematobium  infection과 동반된다

12. localized infection은 impaired local defense ( e.g. effusion, tumor, hematoma ) 가진 area에 more common

Clinical Manifestation

Acute Gastroenteritis

1. incubation period : 6 - 72 hr ( mean, 24hr )

2. abrupt onset of nausea, vomiting,

   & carmpy abdominal pain ( primarily in the periumbilical area & RLQ )

3. mild to severe watery diarrhea가 뒤따름, 때때로 dysenteric diarrhea ( blood, mucus 포함 )

4. moderate fever ( 101 - 102 ℉ ( 38.5 -39 ℃ ) ) : pt의 70%

5. some children

    : high fever, headache, drowsiness, confusion, meningsmus, seizure, & abd. distension

6. stool

    : boody(-), modrate number of PMNL, occult blood

7. Sx

    : healthy children 에서는 2-7일내 subside

    : fatalities - rare

8. neotae, young infants, 1°or 2°immune defiency 가진 children

    : several weeks 동안 sx 지속

Bacteremia 

1 nontyphoidal salmonella동안 transient bacteremia

    : pt의 1∼5%에서 발생

2 salmonella bacteremia는 fever, chills , 때때로 toxic appearance동반

3. prolonged or intermittant bacteremia

    : low-grade fever, anorexia, wt. loss, diaphoresis, myalgia를 동반

<신>4. salmonella gastroenteritis에서 underlying condition을 가진 children는 bacteremia의

        risk가 증가

         table 182-1

<신>5. recurrent salmonella septicemia

       the Centers for Disease Control & Prevention (CDC) care definition에 따른

      AIDS 진단의 criteria 중 하나

       이들환자에서  antibiotics theraphy에 불구하고 recurrent septicemia나타나고

      종종 salmonella에 대한 negative stool culture 와 때때로 infection의 명확한 focus가 없다

<신>6. hemolytic anemia, malaria, bartonellosis

    : increased risk of bacteremia, presumbly because of reticuloendothelial systemic dysfuntion

7. prolonged or recurrent bacteremia

    : schistosomia가진 환자에서

8. pregnancy에서 salmonella septicemia & fetal loss 보고 되기도

9. S. typhimurium

    : U.S.에서 salmonella bacteremia cause의 TMC serotype

Extraintestinal Focal Infection

★Table 182-2

# *▲common focal infection

    ; skeletal system, meninges, & intramuscular sites

# reactive arthritis

    ; HLA-B 27 antigen children에서 salmonella gastroenteritis 후에 발생할 수 있다

5. menigitis

           usually in infants

       little or no fever & minimal symtoms, but rapid deterioration, a high mortality rate (∼ 50% )

       neurologic sequeale

      : occur despite appropriate antibiotic therapy

       also in patients with AIDS

      → mortality rate 50 % ↑

        relaps & brain abscess : occur

6. persistent bacteremia

    : suggests endocarditis, arteritis, or on infected aneurysm

7. the serotypes causing most extraintestinal focal infection

    : s. typhimurium & s. cholerasuis

Asymtomatic Infection

1. after clinical recovery from salmonellar gastroenteritis

    : asymtomatic fecal excretion of samonella

    →for several weeks

2. chronic carries state

    : defined as asymtomatic excretion of salmonella organism for more than 1 yr

3. nontyphoid salmonellosis 후 발생하는 carrier state

       rate ( < 1 % )

       esp in patients with biliary tract ds

4. the only siginificance of asymtomatic fecal excretin of nontyphoidal salmonella

    : the potential transmission of the infection to other individuals

Diagnosis

1. in children with gastroenteritis

  culture of stools

    : higher yields than rectal swabs

2. in patients with sites of local suppuration,

   aspirated specimens → used for gram staining & culture

3. 정상적으로 bacterial flora (e.g. stool ) 를 포함하고있는 specimen은 normal flora의 성장을 억제하는 선택적     인 배지를 사용한다.

    : MacConkey, XLD, bismuth sulfite(BBL) or Salmonella-Shigella(SS) agar

4. rapid diagnosis

   based on latex agglutination & fluorescence

    : available for the rapid dx of salmonella clonies growing

     in stool culture enrichment broth or culture plates

   chromosomal fragments (unique to the genus salmonella)

    : employed as DNA probes to detect salmonella species

5. serologic assay for detecting antibodies agaist s. typhimurium & s. enteritidis

    : reported

Differential Diagnosis

1. the presentation of inflammatory diarrhea with moderate fever

  : diffenentiated from shigella, enteroinvasive E.coli, Yersinia enterocolitica, & Clostridium difficile infection

2. rotavirus infection in infants

3. abdominal pain & tenderness가 심하다면

    : appendicitis, perforated viscus, ulcerated colitis

Prevention

1. chlorinated water, proper sanitary systems, adequate food hygiene practices

    : necessary to prevent nontyphoidal salmonellosis in human

2. handwashing

    : importance in controlling person-to-person transmission by means of food

3. promotion of breast-feeding

    : reduce infection, especilly in developing communities

4. control of transmission of salmonella infection to human

       control of infection in the animal reservoir

       judicious use of antibiotics in dairy & livestock farming

       prevention of contamination of foodstuffs preprared from animals

       use of appropriate standard in food processing in commericial & private kitchens

5. vaccine against nonthphoidal salmonella infection

    :  not  available

Treatment

1. the most important aspects of managing salmonella gastroenteritis in children

       assessment of the hydration status

       correction of dehydration & electrolyte disturbances

       supportive care

2. antimotility agent

       prolong intestinal transit time

       thought to increase the risk of invsion

       not be used when salmonella is suspected

3. antimicrobial agent ( in pt with gastroenteritis )

       not shorten the clinical course

       not eliminate fecal excretion of salmonella

       suppressing normal intestinal flora

    → prolong the excretion of salmonella & increase the risk of creating the chronic carrier state

       used in

        young infants

         increased risk of a disseminated disease

        a severe or protracted course

4. children with bacteremia or extraintestinal focal salmonella infection

    : receive antimicrobial therapy

       ampicillin ( 200mg/Kg/24hr in four divided doses )

       : efficacious & drug of choice

       trimethoprim-sulfamethoxazol

      ( TMR-SMX : 10∼50mg/Kg/24hr im two divided doses )

       chrolamphenicol ( 75 mg/Kg/24hr in four divided doses )

        : effective

       increasing world wide antibiotic resistance of salmonella strain

       → nesessary to perform susceptibility test on all human isolates

5. U.S.에서 salmonella isolates의 약 20%

    : resistant to ampicillin

6. the 3rd-generation cephalosporins

       cefotaxime ( 150∼200mg/Kg/24hr in three to four divided doses )

       ceftriaxone ( 100mg/Kg/24hr in one or two divided doses )

       effective in multiresistance to ampicillin, TMP-SMX, & CM

       not approved for use in children because of the potential damage to growing cartilage

       severe disease 갖고있는 children에서 3rd-generation cephalosporin 으로 initial treatment는 antibiotic

      susceptobility가 알려질 때까지 recommnend

7. duration of antimicrobial therapy

       10∼14 days in children with bacteremia

       4∼6 wks for acute osteomyelitis

       4wks for meningitis

8. in a child with a focal  suppurative process

    : surgical drainge

    → necessary in intravascular salmonella infection

           ( e.g. repair of aneurysm, replacement of valve )

           & in case of chronic osteomyelitis

Prognosis

1. complete recovery

    : the rule in heathy children who develop salmonella gastorenteritis

2. young infants & immunocompromised pt

    : often system involement , a prolonged course & complications

3. prognosis

    : poor for children either samonella meningitis (∼50%mortality rate ) or endocarditis

182.2 Enteric Fever

; systemic clinical syndrome produced by certain salmonella organism

# typhoid fever

    ; caused by S. typhi

# paratyphoid fever

    ; caused by S. paratyphi A, *S. schottmuelleri (formerly S.paratyphi B), S. hirschfeldii (formerly S. paratyphi C) or occasionally other salmonella serotypes

Epidemiology

1. in developing countries

  S. typhi : the most common salmonella isolate

  incidence : 500 per 100,000 (0.5%) & high mortality rate

2. human : the only natural reservoir of S. typhi

    → infection을 위해서는 infected person( sick or chronic carrier )와 direct, indirect  contact가 필요

3. waterborne outbreaks due to poor sanitation & direct fecal-oral spread due to  poor personal hygiene

    : mainly in developing countries

4. U.S.에서 case의 65%가 international travel의 결과

    : Asia (특히 India), central or south america(특히 Mexico) 로의 travel이 transmission

5. enteric fever의 congenital transmission

    : by transplacental infection from a bacteric mother to her fetus

6. intrapartum transmission

    : possible,

      occuring by a fecal-oral route from a carrier mother

Pathology

1. morphologic changes

  young children : less prominent than in older children & adult

2. typical finding

    : hyperplasia of Peyer patchs with necrosis & sloughing of overlying epithelium, producing ulcers

3. the mucosa & lymphatic tissue of the intestinal tract

    : severly inflamed & necrotic

4. hemorrhage

5. inflammatory lesion

   → occasionally penetrate the muscularis & serosa of the intestine

    → produce perforation

6. mesenteric LN, liver, spleen

    : hyperemic , focal necrosis

7. predominant finding

    : hyperplasia of reticuloendothelial tissue with proliferation of mononulear cell

8. mononuclear response

    : seen in the BM associated with areas of focal necrosis

9. bornchitis : common

10. localized abscess, pneumonia, septic arthritis, osteomyelitis, pyelonephritis, endophalimitis, & meningitis

    : inflamatory이 이런형태

Pathogenesis

# blood stream invasion

    --> enteric fever syndrome

# inoculum size required to cause disease

    ; ★10⁵ - 10⁹  organism

3.    ileal brush borders의 microvilli에 attachment (Peyer patches통해)

    → intestinal lymph follicles에 transport

       mononuclear cells내에서 multiplication발생

 

     monocyte   

      : disease process 초기에 bacilli를 파괴할 수 없고 mesenteric LN로 organism 이동

     thoracic duct 통해 blood stream에 도달

    → transient bacteremia 야기

     circulating organism은 liver, spleen, & BM의 reticuloendotheral cell에 도달

    → reitculoendothelial system에서 증식 후 bacteremia의 발생

     GB : blood stream에서 혹은 biliary system 통해 infection 될수 있음

     GB wall에서 local multiplication은 많은 수의 salmonella 형성

    → bile 통해 2차적으로 intestine 에 도달

4. several virulence factors

       surface Vi capsular antigen

           : found in most s. typi

           : interferes with phagocytosis by preventing the bindding of C3 to the surface of the bacterium

           : correlates with invasion capability

       phoP regulon

           : ability of organism to survive within macrophages after phagocytosis

           : related to metabolic effect on host cells

       circulating endotoxin

           : lipopolysaccharide component of bactrial wall

           : thought to cause the prolonged fever & toxic symtoms of enteric fever

       endotoxin - induced cytokine

           : production by human macrophages

           : cause the systemic symtoms

       the occasional occurance of diarrhea

           : by presence of a toxin related to cholera toxin & E.coli heat - labile enterotoxin

5. cell-mediated immunity

    : important in protecting the human host against typhoid fever

6. T lymphocyte ↓ : critically ill with typhoid fever

7. carriers

    : impaired cellular reactivity to S. typhi antigens in the leukocyte migration inhibition test

Clinical Manifestation

# incubation period

    ; 7-14 days (range from 3-30 days)

School- Age Children & Adolescents

1. initial symptom

    : fever, malaise, anorexia, myalgia, headache, abdominal pain

    → 2 ∼ 3일에 걸쳐서 발생

2. diarrhea

       a pea soup consistency

       during the early course of the disease

       later → constipation 이 more prominent symptom

3. N/V : uncommon

4. cough, epistaxis

5. severe lethargy

6. fever

       rise in a step-wise fashion

       intermittent, high within 1 wk, reaching 40℃ ( 104℉ )

7. during the 2nd wk of illness

       sustained high fever

       fatigue, anorexia, cough, abd. symtoms : severity ↑

8. acutely ill, disoriented & lethargic         

9. delilium, stupors, relative bradycardia

10. hepatomegaly, splenomegaly, distended abdomen with diffuse tenderness

           : very common

11. rose spot

       enteric fever 환아의 50%에서

       macular or macularpapular rash : 7th to 10th days

       lesion : discrete, erythromatous, 1 ∼ 5 mm in diameter

       slightly raised, blanch on pressure

       crops in 10 to 15 lesion on the lower chest & abdomen , last 2 or 3 days

       slight, brownish discoloration on the skin on healing

       cultures of the lesion

    : 60% for salmonella organism

12. no complication시

    sx 과 physical finding은 2∼4주내에 resolve, malaise & lethargy는 1∼2개월 더 지속될수도 있다

Infants & Young Children (<5 Yr)

1. rare

2. mild fever & malaise, misinterpreted as viral syndrome

3. diarrhea

    : more common in young children

           → leading to a diagnosis of AGE

4. lower respiratoy tract infection 의 sn & sx

Neonates

1. abortion & premature delivery야기

  late pregnancy 동안은 vertical로 transmit

2. ds는 delivery 3일내에 시작

3. vomiting, diarrhea, abdominal distension : common

4. temp ; variable

5. seizure, hepatomegaly, jaundice, anorexia, & wt loss

Laboratory Findings

    ; normochromic, normocytic anemia

           - related to intestinal blood loss or BM suppression

    ; frequently low WBC counts in relation to the fever & toxicity

          - *lekopenia : not below 2500 cells/mm3

           - often seen after the 1st or 2nd wk of illness

    ; *leukocytosis 

           - 20,000-25,000 cells/mm3

           - *pyogenic abscess develops

    ; *thrombocytopenia

           - striking & persist for as long as 1wks

    ; LFT : often disturbed

    ; *proteinuria

    ; fecal leukocytes & fecal blood : very common

Complications

; intestinal perforation, myocarditis, CNS symptoms

; *usually occur after 1wks of disease

# severe intestinal hemorrhage (1-10%) & intestinal perforation (0.5-3%)

    ; perforation

          - distal ileum typically

          - marked increase in abd. pain, tenderness, vomiting & sign of perforation

4. sepsis with various enteric aerobic Gr-negative bacilli & anaerobes

5. overt hepatitis & cholecystitis

6. clinically obvious pancreatis

7. pn

    : adult보다는 children에 common하여 다른 organism에 의한 superinfection으로 야기

8. toxic myocarditis

    : arrhythmia, sinoatrial block, ST-T change on the EKG, cardiogenic shock, fatty infiitration,

     necrosis of myocardium    

9. thrombosis, phlebitis : rare

10. neurologic Cx

    : ICP ↑, cerebral thrombosis, acute cerebral ataxia, chorea, aphasia, deafness,

      psychosis, transverse myelitis

11. peripheral & optic neuritis

12. fetal BM necrosis, PN, nephrotic syndrome, meningitis, endocarditis, parotitis, orchitis,

    & lymphadinitis

13. osteomyelitis & septic arthritis

    : more frequntly in children with hemoglobinopathy

Diagnosis

# bood culture

    ; *40-60% in early state

# stool & urine culture

    ; *positive after 1st wk

# stool culture

    ; occasionally positive during incubation period

# BM culture

    ; *▲sensitive method of diagnosis

           - *positive in 85-90%

    ; often positive during later stage

           - mesenteric LN, liver, spleen의 culture에서도 (+) 일수 있다

    ; less influenced by prior antimicrobial therapy

# suspected case with negative stool culture

    : culture of aspirated duodenal fluid or of a duodenal string capsule

    → helpful in confirming infection

# identification of S. typhi from culture

    ; 적어도 3일

# ★PCR (polymerase chain reaction)

    ; amplify specific genes of  S. typhi in the blood of patients

    ; *diagnosis with a few hours

    ; specific & more sensitized than blood culture given the low of bacteremia in enteric fever

# the classic widal test

    ; antibodies against O & H antigen

    ; many false-positive & false- negative results

           --> widal test 하나만으로의 typhoidal fevers 진단은 error 경향이 있다

Prevention

# in endemic areas

  ; ★improved sanitation & clean, running water

           - *essential to control enteric fever

    ; personal hygiene measures, handwashing & attention to food preparaion practice

    ; eradication from carrier

# parenteral heat-phenol-inactivated vaccine

    ; limited protection ( 51-76% efficacy )

    ; associated adverse effects

           - fever, local reaction, headache in at least 25% of recipients

    ; 10 세 이상 - 0.5ml subcutaneously, two doses, 4wks or more

  ; 10 세 이하 - 0.25ml

# second newly licensed vaccine (Vivotif)

       oral, live- attenuated preparation of the Ty21a strain of S. typhi

       efficacy ( 67 ∼ 82 %)

       siginificantly adverse effects : rare

       four enteric-coated capsule on alternative days

       limited expensive 때문에 6세 이하에서는 not recommend

       immunodeficiency syndrome에서는 not use

# travels to endemic areas (esp Latin America, Southeast Asia, & Africa )

    ; typhoid vaccine recommend

           - *vaccine efficacy 100 % 아니므로 personal hygiene과 food & dirnk selection이 더중요

Treatment

# mostly antibiotic regimen

    ; *5-20% recurrence

# documented good clinical efficacy

    ; chloramphenicol 50 mg/kg/24hr po or 75 mg/Kg/24hr IV in four equal doses

          - more rapid defervescence & sterilizatin of blood

           - *higher relapse rate

    ; ampicillin 100 mg/kg/24hr po in three doses

    ; amoxillin 100mg/kg/24hr po in three doses

    ; trimethoprim-sulfamethoxazole

           - 10mg of TMP & 50 mg of SMX/kg/24hr po in two dose       

# Tx course

    ; mostly afebrile within 7days

    ; *at least 14days or 5-7days after defervescence

    ; 21 days if underlying disturbance such as severe malnutirion

# ★Resistant Strains

    ; usually susceptible to third-generation cephalosporins

    ; cefotaxime 200mg/kg/24hr IV in three to four doses

    ; ceftriaxone 100 mg/kg/24hr IV in one to two doses

           - somewhat better response

# ♣aztreonam, fluoroquinolone

    ; *efficacious, not approved for children

# ★ciprofloxacin

    ; in adult

    ; 500mg twice daily for 7-10days

    ; effective & low relapse rate

# dexamethazone

<신>   using 3mg/kg for the initial dose,

        followed by 1 mg/kg every 6 hr for 48 hr

        improved the survival rate of patients with shock, obtundation, stupor, or coma

        antibiotic therapy가 적절하다면 complication incidence를 증가시키지는 않는다

6. supportive treatment & maintence of appropriate fluid & electrolyte

    : essential

7. intestinal hemorrhage가 severe

    : blood transfusion

8. surgical intervention with broad-spectrum antibiotics

    : intestinal perforation

9. platelet transfusion

    : suggested for the tx of thrombocytopenia

      → severe to cause intestinal hemorrhage in patients of whom surgery is contemplated

# ★Tx Of Chronic Carrier

    ; course of 4-6 wk of high-dose ampicillin (or amoxicillin) plus probenecid or TMP-SMX

    ; 80% cure rate if no biliary tract disease

    ; ciprofloxacin

          - used successfully in adults

    ; if cholelithiasis or cholecystitis

           - *cholecystectomy within 14days of AB treatments

Prognosis

1. depends on

       prompt therapy

       the age of  the patient

       previous state of health

       the causative salmonella serotype

       the appearance of complications

2. developed countries 에서 적절한 antimicrobial therapy 시

    → mortality rate는 1% 이하이다

3. developing countries 에서 mortality rate는 10% 이상이다.

    → diagnosis, heospitalization, treatment의 지연때문이다

4. high risk

       infants younger than 1 yr of age

       children with underlying debilitating disorders

5. appearance of Cx

       gastrointestinal perforation or severe hemorrhage, meningitis, endocarditis,  pneumonia

       associated with high morbidity & mortality rate

6. relapse & mortality rates

       relapse after the initial clinical response

       : 4∼8% of the patients ( not treated with antibiotics )

       적절한 antibiotics tx 받은 환아에서 relapse의 clinical  manifestation은 항생제 중단후 

       2주경에서 나타나고, acute illness 와 혼동

       usually milder & shorter duration

       multiple relapse 있을수도 있음

7. chornic carrier

       S. typi를 infection 후 3개월 이상 excrete하는 indivudual은 1년정도에서 보통 excrete되고

       chronic carrier로 정의     

           typhoid fever 모든환아에서 1∼5 %

       biliary tr ds의 incidence는 chronic carrier에서 general population보다 높다

8. chronic urine carriage가 발생할 수 있고 rare하여, 주로 schisosomiasis 가진 환아에서 발견

Chapter 183. Shigella

# 4 species of shigella are respons for illness

    1) S. dysentriae (serogroup A)

    2) *S. flexneri (Serogroup B) - ▲common

    3) S. bodyii (Serogroup C)

    4) S. sonnei (Serogroup D) - increasing pattern

Pathophysiology

1) Basic virulence trait as ability to invade colonoc epith. cell

       이 특징은 large plasmid (120-140 megadalton) on encoded 되어있고

       polypeptide group (cell invade & kill)의 synthesis에 responsible.

       E. coli에서도 Shigella의 plasmid와 유사한 것 있다.

2) Chromosomally encoded factors.

     Also required for full virulence.

     Lipopolysaccharide의 synthesis와 연관. shigella에 중요.

3) Shiga toxin

     a potent protein Syn. inhibiting exotoxin.

       only produced by S. dysenteriae serotypeⅠ & EHEC. Shiga-like toxin producing E. Coli

     shigellosis의 watery diarrhea는

    a. SHET-1 : encorded on the bacterial chromosome

    b. SHET-2 : encorded on the virulence plasmid.

# *very low inocula cause illness

    ; S.dysenteriae serotype 1

           - *as few as 10

Immune Responses

  1. Secretory IgA & Serum Ab - infection 수일 - 수주 내에 develop

          Subsequent infection & anti virulence plasmid의 major determinants로서 anti- polysaccharide & 

          antivirulence polypeptide Ab의 identification을 아직 unclear.

          protection이 serotype specfic 함 but All strain of Shigella에 대한 Cross-protection도 어느정도 suggest됨.

  2. Cell med. immunity

    : also play some role in immunity but minor.

Pathology

    ; *Colon

           - *primary pathologic changes & target organ

   ② most intensive changes ; distal colon, pancolitis도 일으킬 수 있다.

     ③ Grossly ; Localized or diffuse mucosal edema, ulceration. friable mucosa. bleeding exudate가 나타난다.

     ④ microscopically ; ulceration, pseudomembranous, epithelial cell death. nucosa에서 muscularis mucosa에 PML, mononuclears cell들이 infilteration. submucosal edema가 생김.

Epidemiology

     warm months in temperate climete rainy season in tropical area

     sex ratio : equal

       age : at any age, peak : 2-3 yr of life

      6 Mo 이하에서는 rare. 이유는 unclear

          ; endemic area에서 breast milk내에 virulence plasmid-coded Ag과             

         lipopolysaccharides 에 대한 Ab가 있는 것이 age-related incidence에 부분적으로

    ; ★S. sonnei

           - *▲common in industrialized societies

    ; S. flexneri

           - *▲common in preindustrialized societies

    ; *Contaminated food & Water is important vector

    ; *Person to person transmission is major mechanism

Clinical Manifestations

    ; Severe abd. pain, high fever, emesis, anorexia, generallized toxicity, urgency, painful defication

  ; abd. distension, tenderness, hyperactive bowel sounds, tender rectum on physical exam.

    ; Diarrhea

        - initially watery & large volume

         --> evolved to frequent, bloody mucoid, small volume stools

           - chronic diarrhea uncommon

    ; dehydration

# Neurolcgic findings

    ; *▲common extraintestinal menifestation

    ; *more than 40%

    ; convulsion, headache, lethargy, confusion, nuchal rigidity, hallucination

    ; seizure

           - before or after diarrhea

           - 원인

                   / 현재는 shigatoxin, meningitis에 의한 것이 아니라고 생각되고 있다.

                   / *hypocalcemia, hyponatremia에 의한 것으로 생각하고 있다.

# Complication

    ; ★Dehydration

           - *▲common

           - attendant risks of renal failure & death.

      ; SIADH

    ; sepsis

           - more common S. dysenteriae type 1

           - mortality : 20-50%

    ; DIC

    ; uncommon Cx

           - Rectal prolapse, Toxic megacolon, Pseudomemb. colitis(esp. S. dysenteriae), Cholestatic hepatitis, Conjunctivitis, Iritis, Conrneal ulcer, Pneumonia, Arthritis(enteritis 2-5주 후), Reiter synd., Cystitis, myocarditis, Vaginitis (S. flexneri, bloody discharge)

    ; ♥Ekiri Syndrome Or “Lethal Toxic Encephalopathy”

        - rale extreme toxicity

           - Convulsions, Hyperpyrexia, headache followed by brain edema, rapidly fatal outcome without sepsis or significant dehydration

# S. dysenteriae type 1 infection common Cx.

  ; hemolysis, Anemia, Hemolytic Uremic syndrome

Diagnosis

 1) Clinical features

      clinical feature가 shigellosis를 suggest하더라도 Insufficiently specific to allow confident Dx.

        Confusion with EIEC, EHEC, Salmonella, Camphylobacter jejuni, Y. enterocolitica,

        E. hystoritica, inflammatory bowel ds.

 2) Laboratory

      Often not able to confirm the clinical suspicion of Shigellosis.

       Presumptive Data : supporting a Dx.

      fecal leukocytosis (confirming the presence of coilitis)

      peripheral blood smear : dramatic left shift (more band > seg)

     보통 5000-15000/㎣, 때로 Leukopenia & Leukemoid Rx (+).

 

  3) c/s of both stool & rectal swab.

      Optimizes the chance of diagnosing Shigella infection.

      c/s media : a. MacConkey agar

                  b. Xylose-lysine deoxycholate agar.

                  c. SS agar.

      적절한 media 사용으로 Campylobacter와 다른 Agent 배제해야 한다.

      culture가 good standard for Dx. but it is not absolute.

      : 20%에서 stool c/s상 failed.

        Single c/s로서 Shigella pt.의 약 50%에서 Dx (Blood c/s 50%, stool c/s 50%)

  

       ※ Very young infants or malnourished infants에서 toxic app 해 보이면 blood culture를 꼭

           시행해야 한다. 왜냐하면 Bacteremia의 risk ↑↑.

Treatment

# Fluid & electrolyte correction & Maintenance

# *drugs retarding intestinal motility

    ; *contraindication

# AB medication

    ; Ampicillin   

           - resistant

    - if susceptible, 100mg/kg/24hr #4

    ; TMP-SMX

           - often resistant

           - usual empric choice prior to availability of susceptibility

       - TMP 5-10mg/kg/D #2

    ; Quinolone

        - in adults

    ; *cefixime (8mg/kg/D #2 po for 5day), ceftriaxone (50mg/kg/D sngle Ⅳ for 2-5 days)

    ; Nalidixic acid

       - 55mg/kg/D #4 po for 5 day

※ Ampicillin sensitive pt.에서 Amoxicillin은 Ampicillin보다 덜 민감하다.

※ Shigella Dx.에 있어 아직은 stool c/s가 confirm하는데 most helpful.

         pathogen의 isolation 없으면 least helpful.

※ Typical dysentery (+), initial empiric ABT Tx에 반응 (+) 시 stool c/s (-)라도 5 day full course의 ABT Tx 해야함.

- 이유는 ① Shigella의 c/s가 어렵고

② EIEC와 구분이 잘 안가고

③ Routine clinical microbiology Lab 상 Dx.(-) 때문.

※ 처음 c/s(-)인 pt.에서 Tx.에 실패시 culture는 다시 시행되어야 하고 다른 가능한 진단을 위해 Re-evaluation해야 한다.

Prevention

※ Shigellaosis를 줄일 수 있는 2 simple measures.

1) Encourage prolonged breast-feeding.

     ; Shigellosis의 risk ↓, infection 시 severity ↓

    2) Educate family in handwashing technique (특히, defecation 후와 음식식사전이나

                                      음식 조리전에)

3) Other public health measures

   : water & sewage treatment.

Chpater 184. Escherichia Coli, Aeromonas, And Plesiomonas

Escherichia Coli

Etiology and Pathogenesis

Enterotoxigenic E. coli (ETEC)

# ★Heat-Labile Enterotoixn(LT) And/Or Heat-Stable Enterotoxin(ST)

    ; *not injury or kill cells

           --> disturb cyclic nucleotide-regulated fluid & electrolyte absorption

    ; LT

           - related with cholera toxin by V. cholerae

           - stimulation of guanylate cyclase

                   --> increased cyclic GMP

    ; ST

           - related with enterotoxin by Y. enterocolitica

           - stimulation of adenylate cyclase   

                   --> increased cyclic AMP

# ★Fimbriae

    ; allow them to adhere tightly to intestinal epithelium

           --> effectively colonization and delivering toxin

# different colonization factor antigens (CFA)

  ; important in affecting the adherence of ETEC

  ; CFAⅠ, CFAⅡ, Ⅲ,Ⅳ, CS7, CS17, 2230, 8786, PCF 09, PCF0148, PCF 0159, PCF 0166

  ; genes for both colonization factors & enterotoxin are typically encorded on the same plasmid 170여 serotype 중 ETEC와 관련된 것은 소수

Enteroinvasive E. coli (EIEC)

    ; invasion of gut epithelium

           --> dysentery like illness

# ★Large Virulence Plasmid

    ; produce small group of polyeptide : critical role to invasion of intestinal epithelium

           --> invasion

           --> cell death & brisk inflammatory response

           --> clinically recognizable as colitis

# ★Lipopolysaccharide (LPS) Ag like shigella LPS

# non motile (lack H or fragella Ag) & usually nonlactose fermentes

Enteropathogenic E. coli (EPEC)

    ; belongs to serogroups(O Ag or LSP Ag)

    ; *asso. with outbreaks of infantile gastroenteritis

    ; *no producing enterotoxins & invasion epithelial cell

    ; adherence to intestinal mucosa in a distinct way

           - trasmission EM findings

           / ★"close attaching & effacing" adherence or "Pedestal forming" adherence

    ; *adherence to HEp-2 cell assays

           - localized adherence

                   / attach loosely microvilli of the epithelial cell through ropelike structures(called *bundle-forming pili : encorded on a EAF plasmid)

             --> ★eae gene ( E. coli attaching-effacing ) action

                           --> epithelial cell에 attach.

          : EAF probe ( + )

           - diffusely adherence

                   / produce *adhesin (AIDA-1 : homology to S. flexneri protein)

                           --> intercellular spread ( Vir G )

           EAF probe ( - )

Enterohemorrhagic E. coli (EHEC)

# entericytotxic E. coli

    ; produce one or more toxins that kills mammalian cells

    ; =shigella-like toxin-producing E. coli (SLT-EC), verotoxin-producing E. doli (VTEC)

# ★Two Major Toxin

    1) shiga-like toxin I(SLT-I)

           - identical to shigatoxin(protein synthesis-inhibiting enterotoxin of shigella dysenteria serotype I)

    2) shiga like toxin II (SLT-II)

           - more distantly related to shigatoxin (only 55y. ammoacid homology)

  ; multiple varient to these toxin are exist

  ; *kill cells by cleaving an adenine residue from ribosomal RNA

       --> protein syntheis inhibition cell death.

# EM findings

    ; EHEC가 intestinal wall에 붙어 lesion을 형성하는 것이 EPEC에서 와 유사하지만 more restricted in there distribution

  ; EHEC : formed primarily in the colon

    ; EPEC : infest the entire intestine

Enteroaggegative E. coli (EAggEC)

    ; adhere to HEp-2 cell and colonic epithelial cells

           - by ★plasimd-encoded aggregative adherent fimbriae (AAF/1)

           - not possess eae gene or produce attaching-effacing lesions

# two toxin

    ① 4.1KD heat-stable toxin EAST1 encaded on a plasmid

    ② 120KD heat labile protein

                ; related to the pare-farming ? toxin fauily ; utracellular ca 9

Epidemiology

    1) inc. frequency in during warm months in temperate climate

       during rainy season in tropical climate

    2) 1st few yr of life에 多

       3) most E. coli (예외, EHEC, some EPEC) require large inculum of organism to induce disease

# EHEC, EPEC

    ; *person to person spread & food spread

           - *lower organism ingestion suffient to cause diseases

# ★poorly cooked Hamburger

    ; *▲cause of food-borne outbreak of EHEC

Pathology

    1) ETEC : no structural alteration in the mucosa

    2) EIEC : bacillary dysentery 같은 colonic cause의 원인이 됨

            : ulceration, hemorrhage, PMNL infiltration. mucosal & submucosal edema

# EPEC

    ; vili의 blunting. LM상 superficial mucosal cell의 sloughing & inflammatory change :       

                 duodenum - colon에서 보임. EM상 attaching and effacing change

      4) EHEC :affect the colon most severely. edema, fibrin deposit, submucosal hemorrhage,

                mucosal ulceration, neutrophile infilteration, microvascular thrombi.

                shiga like toxin과 LPS의 lipid A protein의 synergistiic action 에 의해 야기

    5) EAggEC : heat stable or heat labile toxin 에 의해 야기

㉿Clinical Manifestation

# ETEC

    ; major cause of dehydrating infantile diarrhea

  ; explosive watery diarrgea, abdominal pain, nausea, vomiting, little or no fever

# EIEC

    ; classic bacillary dysentery-like illness

    ; fever, systemic toxicity, crampy abdom6inal pain, tenesmus, urgency, watery or bloody diarrhea

# EPEC

    ; *infant, children in the 1st few yrs

    ; *no blooy diarrhea with mucus

    ; fever

    ; *prolonged diarrheal disease

# EHEC

    ; nondescript diarrheal illness

  ; abdominal pain with diarrhea

           - initially watery but within a few days grossly bloody

           --> hemarrhagic colitis

    ; *fever - uncommon

    ; 10% hemolytic uremic sydrome

# EAEC

    ; significant fluid loss with dehydration

    ; infrequent vomiting, grossly bloody stools

    ; *asso. with prolonged diarrhea

Complication

# major Cx ; dehydration & electrolyte loss

# *EPEC, EAEC ; persistent diarrhea

# *EHEC ; hemolytic uremic syndrome

Diagnosis

   1) clinical features : seldom distinct enough to allow confident Dx.

   2) routine lab. : very limited value

                 routine stool c/s : reveal only 'normal flora'

                 biochemical critera (fermentation pattern) : minimal value

     ※ EHEC Sewtype 157 : H7 : failure of a suspect colony to fermenent sorbital on MacConkey sorbitol medium

     ※ latex agglutination : O 157 LPS containing organism 27 confirm.

     ※ c/s of duodenal fluid

   1. helpful in Dx. of EPEC (by tendency to colonize the small intestine)

   2. only indicate in chronic diarrhea child

     ※ Fecal leukocyte : (+) only in EIEC

     ※ Blood counts (CBC) : leukocytosis with Left shift in EIEC. EHEC.

 

      3) Electrolyte : fluid loss만 반영할 뿐 nonspecific

 

     4) Animal or tissue c/s - cumbersome and expensive for routine use.

  * 이론적으로는 EPEC가 serologcally identified. 그러나 실제로는 Cross Reaction으로 큰 의의 없다.

Treatemnt

    1) 원칙 : fluid & electrolyte therapy by oral replacement & maintenance Rehydrating sdol'n

         : Early refeeding with breast milk or dilute formula 권장

         ※ ( 비록 early refeeding이 Diarrhea를 악화시킬 수 있다 하도라도 prolonged witholding of              

            feeding이 chronic Diarrhea and malnutrition을 유발할 수 있기 때문에)

  2) ABT treatment - problematic !!

       (왜냐하면 pathogen 의 accurate Dx나 ABT suscepectibility의 불예측성때문)

   1. ETEC : TEMP-SMX에 respond (그러나 최근에 developing world를 여행하고 돌아온

              severe watery diarrhea를 가진 child에서는 적당하지 않다.) 

   2. EPEC : TMP-SMX [(6.4㎎/㎏/d Ⅳ qid or oral qid) × 5 day]

            = effective in speeding resolution

            : rapid Diagnostic test 수행 (-)    Tx Decision is Difficult.

   3. EIEC : c/s Result의 유용성 정도에 관계없이 만약 organism에 susceptible하면 TMP-SMX 쓴다.

   4. EHEC : particulary difficult therapeutic Dilemma

             (Sulfa containing ABT Tx    Hemolytic Uremic Syndrom risk↑)

   5. EAEC

  ※ Prophylactic ABT Tx

       : Adult treveler에서는 effective, but Children에서는 not been studied, not generally recommende.

    3) Public health measure

     : sweage disposal and food handling practice

Prevention

  1) mantaining prolonged breast-feeding

  2) paying careful attention to personal hygiene.

  3) proper food, water handling procedure

Aeromonas

; cold-blooded and warm-blooded animals에서 야기하는 ds.

; cold-blood animals ; nonmotile, psychrophilic species,

  warm-blooded animals ; motile, Mesophilic.

; Human ds를 야기시키고 species.

  A. hydrophila, A. sobria, A. caviae

Bacteriology

   ① oxidase (+) facultatively anaerobic.

   ② G(-) rods,

   ③ family Vibrionaceae.

   ④ cytochrome oxidase (+) ; enterobacteriacae 와 구별.

   ⑤ blood agar, MacConkey agar에서 쉽게 cultivated.

     ⑥ selective Media ; alkaline peptone water

                      blood agar, contaming ampicillin.

                      cefsulodin - irgasan - novobiocim agar

Epidermiology

   ① G1 infection : well water and pretreatment with antibiotics water의 ingestion과 관계

   ② wound infection : contamination by enviromental water과 관계

   ③ warm weather

   ④ symptomatic & asymptomatic infection (+)

Pathogenesis

     ① A. hydrophilia A. sobria ; hemolysin cytotoxins, enterotoxins poduce

      ; HEp-2 as on invade.

         mucosa 에 invade    bacteremia in animal models.

Clinical Manifestation

   ① Gastroenteritis (MC)

     ㉠ acute diarrhea pt의 2-10%에서, isolated asymptomatic control 의 1-5% isolated

     ㉡ A. caviae ≫ A. hydrophilia A. sobria 

        ㉢ 대부분 watery diarrhea (cholera like 10-30%에서는 dysentry like febrile diarrhea with bloody strool.    

        ㉣ fecal leukcytes ; unusual

      ② septicemia

      ; 다른 underlying disease가 있는 pt에서 볼 수 있다

      ; mortality rate : 30-70%로 high

        ; trauma, Respiratory tract infection 후 immunocompetent host에서 occurs                    

         A. hydrophilia, A. sobria가 septicemia 의 most common species.

      ③ penetrating trauma or apen fx시 contaminations

      purulent soft tissue infection

      cellulitis, fulminating myonecrosis

Treatment

; treated control study 가 없다.

   1.  dysenteric form ; Trimethoprime - surfamethoxazole : 효과

   2.  septicemia ; Aminoglycosides 또는 3세때 cephalosporins

Plesiomonas Shigelloides

  ; reported in sporadic cases and outbreaks of diarrheal disease.

  ; oysters와 같은 food ingestion 과 연관이 있다.

  ; vrirulence factor로 잘 반응

  ; bloody diarrhea와 antibiotics에 잘 반응하는 high fever.

Bacteriology

   ① G(-), non-spore-forming

   ② facultatively anaerobic, indole producing slow lactase fermenters, catalase(+)

   ③ 2-7개의 polar flagella.

       ④ enterobacteriaceae와는 oxidase(+)로 구별되고 ornithine decarboxylese(+)와 inositol            

           fermentation으로 Vibrionaceae와 구별

   ⑤ serotype C27 : LPS(+) ; shigella sonnei phase 1 LPS와 antigenically : identical.   

    2) pathogenesis and Pathology

    enteroinvasiveness in mechanism.

    virulence traits는 잘 모름

Epidermiology

   ① warm month

   ② 해산물 (특히, 생굴), 여행후에 발생

   ③ 5세이하에 increased.

Clincal Manifestations

   ① watery (c/s blood in the stools) diarrhea.

   ② fever is common

   ③ abdominal pain, Vomiting ; frequentry.

   ④ illness ; last 1-2 wk

      ⑤ bacteremia, cellulitiis, meningitis (특히 neonates)

    다른 extraintestinal manifestations.

    ; 주로 immunocompromised host에서

Diagnosis

     Routine stool culture.

     fecal leukocytes.

Treatment

    1. Gastroenteritis ; self-limited. no therapy가 recommended.

    2.  TMP- SMX : bloody diarrhea나 persistent diarrhea 에 use.

    3.  extraintestinal infection ; Aminoglycoside

184.1 Infections Due To Pseudomonas

; abundantly in soil & water

; *mostly opportunistic infection

# ★Increased Risk Groups

    ; low-birth weight infants

  ; old infants & children with impaired with host defences

       - cystic fibrosis, immunodeficiency disorders, malignancies, extensive burns, malnutrition, receving immunosuppressive Tx

Etiology

    많은 species 중 소수만 pathogenic ( mc P. auroginosa )

    ; *G( - ) rod strict aerobes

    90%이상에서 blood agar 에서 B-hemolysis --> bluish-green phenazime pigment 형성       ( blue pus )

Epidermiology

       frequently enter the hospital enviroment.

       prolonged hospitalization

       broad spectrum antibiotics의 사용

       chemotherapy

       Mechanical ventilation

       urinary catheter의 사용

Pathogenesis

       skin infection --> endotoxin --> local necrosis, bacterial invasion

       exoenzyme S is another toxic virulent facter.

       Pseudomonas produces disease by three stages.

       i) bacterial colonization and attachment

       ii) dissemination and bloodstream invasion

       iii)host responds : Ab to pseudomonas exotoxin ( exotoxin A ) and  lipopolysaccharide.

Clinical Manifestation

★Table 184-1

   # Pseudomonas infection 에서 skin의 특징

       skin lesion은 water source 와 접촉 수 시간 -- 2 일 후 발현

       erythmatous, macular, papular, pustular

       very from a few scattered lesion to extensive truncal involvement

    * 특징적 findings

      pink macule로 시작되어 hemorrhagic nodules이 되고 eschar formation을 가진 necrosis가 될 수 있다.

    * P. aeruginosa외에는 healthy children에서

      P. cepacia : pneumonia, abscess

      P. putrifaciens, P. stutzeri : otitis media

      P. fluorescens : abscess

      P. maltophilia : cellulitis, septicemia, endocarditis : intravenous drug abuse와 관계.

    * burns and wound infection

      burn pt 에서 P. aeruginosa에 의한 septisemia가 major problem

   # malignancy

    1. immunosuppressive therapy --> neutropenic 하고 extremely pseudomonas에 susceptible해진다.

    2.  generalized vasculitis --> all organ hemorrhagic necrotic lesion

        -->  purple nodule, ecchymotic area 

        --> gangrenous --> hemorrhagic or gangrenous perirectal cellulitis, abscess.

Prevention

# newborn nurseries infection

    ; transmitted by hand of personel

       따라서 strict attention to hand washing and rinsing catheter 는 3% solution of acetic acid.

# burn pt's

    ; *polyvalent Pseudomonas vaccine

           --> reduce of bacteremia, mortality

    ; *specific hyperimmune globulin

           --> prevention of septisemia

# careful protective isolation

       : topical application of surfadiazine.

        10% mafenide acetate cream, debridment.

Treatment

    1. response to Tx. may be limited.

    2. compromised host 에서 systemic infection에 대한 prolonged Tx.필요.

   # septicemia

        carbenicillin : 200-400mg/kg/24hr # 6

        or ticarcillin : 200mg/kg/24hr # 6 iv

        G-M : 5-7.5 mg/kg/24hr # 3

        : synergistic effect 때문에 꼭 사용

         생후 1 wk후에는 high dose로 사용

          iv, im 가능하고, 1 hr이상 걸쳐 slowly infused.

        Carbenicillin 과 Ticacillin은 단독사용은 resistant가 빠르게 나타나므로 Rec. 되지않음.

        Tobramycin : 3-5mg/kg/24hr  or Amikacin : 15-25mg/kg/24hr # 3 im, iv

        가 G-M 대신 사용되기도 함.

Prognosis

        Leukemia의 leading cause of death가 septicemia이고 그 중 1/2 이 pseudomonas 이다.

        Peudomonas auroginosa에 의한 septicemia는 combined antimicrobial therapy에의해서 improved된다.

        P. cepacia는 standard antimicrobial agents 에 frequently resistant 하고 pulmonary           

        function을 rapidly decline시키고  survival도 낮다.

        pseudomonas meningitis 는 치료후에도 몇몇 infants 에서는 normal development가 poor하다.

Disease Due To Other Pseudomonas

Glanders

:    horses에 P. mallei 에 의한 severe infectious disease로 man에  transmitted 될 수 있다.

                     Asia, Africa, middle east에 많다.

                     acute or chronic pneumonitis

                     skin, nasl, mucus membrane, lymph node 에 hemorrhagic necrotic lesion을

                     Tx: TC, CM, SM을 몇달 이상 사용

Melioidosis

      i) endemic area : southeast asia, northern australia, US

      ii) direct contamination or dust inhalation에 의해 야기.

      iii) single primary skin lesion : vesicle, bulla, urticaria

      iv) pulmonary infection은 subacute, Tb와 비슷.

      v) 때때로 septisemia, multiple abscess야기

      vi) encephalitic illness : fever, seizure도 올 수 있다.

      vii) initial exposure 몇년 후 host resistance가 떨어지면 발병

      viii) Tx. : ceftazidime, CM with Doxycycline and TPM-SMX.

Chapter 185.  Cholera

    # 1990년대에 V. cholera 의 new virulence gene이 발견되었고 V.cholera의 new,               

      unique strain이 epidermic의  spread에 관여하는것을 밝힘.

    # V. cholerae serotype O1 or O139( Bengal ) 에 의해 생산되는 enterotoxin의 group 에 의해

      acute watery diarrhea 유발

    # Clinical spectrum : asymptomatic, mild watery diarrhea, severy watery diarrhea with vomiting

        --> rapidly hypovolemic shock, metabolic acidosis, death

Etiology

      G(-) non-spore forming, motile, slightly curved rods. pollar flagellum

      growth in alkalin media with bile salt

      V. cholerae O1 : classic, EI Tor

      Somatic antigen에 의해 serogroup으로 나눔

       - major antigenic type ( Ogawa, Inaba )

       - unstable intermediate type ( Hikojima )

      new epidermic strain, V. cholerae O 139 ( Bengal )

       - O1 antiserum과 agglutination이 안됨

       - E1 Tor biotype과 밀접한 관계가 있다.

Epidermiology

      V. cholerae organism, survive in warm, saltly water with nutrients and oxygen

      direct person to person transmission은 rare

      endemic area에서 2-15yrs children에 affect

      2yrs이하에서 breast milk가 severe cholera로 부터 protecting.

      1991 : peru에서 발생하여 남,중미지역으로 rapidly spread

      1993년까지 820,735 cases 중 6942명이 사망

      low case - fatality rate ( 0.8 % ) ; virulence의 감소 보다 치료의 성공에 의해.

      특징 : i) rapid spread

            ii) high attack rate

            iii) low mortality rate

    6. 1992 : India 에서 new serotype V. cholerae O 139 가 O1 외에 1st epidermic cholera 를 야기.

       1993년 첫 3.5 months동안 13275명의 환자 중 434명이 사망.

       특징 : i) new strain이 more hardy하고 transmission의 greater risk를 가짐.

             ii) secondary infection의 frequency가 높다.

             iii) asymptomatics에 대한 symptomatic infection의 ratio가 높다.

             iv) adult에 high attack ratio를 보였다.

Pathology and Pathophysiology

        Vibrio는 acid에 매우 sensitive하다. 따라서 stomach은 organism이 small bowel

               에 도달하는 것을 막는 매우 효과적인 barrier이다.

         Vibrio는 disease를 야기시키기 위해서는 small bowel에 colonize해야만 한다.

          --> small bowel mucosa에 attack, proliferate --> mucinase와 같은 proteolytic enzyme을생산,

          motility도 중요한 virulence trait ---> duodernum, jejunum에 colonization  --> clinical feature.

     * villi tip의 capillary, lymphatics edema ---> dilated.

     * lamina propria에 a few inflammatory cell

         fluid lost : isotonic, bicarbonate, potassium의 high concentration

                 ; bacterial chromosome에 encorded 되어 있는 enterotoxin에 의해서 야기.

                 ; enterotoxin --> cAMP의 prolonged elevation

                --> villous cell에서 Na, Cl 의 active absorption의 감소, crypt cell에서의 Cl의  secretion의 증가.

         2nd toxin : genetically engineered strains with a delation of cholera toxin A subunit

                ( Zonula occludens toxin , Zot )

                   --> intercellular tight junction을 alteration

                   --> interstitial mucosa가 more permeable 해지고 hydrostatic pressure에의해 lumen으로

                        water, electrolyte의 leakage

                   -->diarrhea야기.

     * 3rd portential enterotoxin ( accessory cholera enterotoxin ,ace )

                 : leukocytic - ion - transporting APTases 와 매우 흡사.

     * ctx, zot, ace genes : " virulence cassette " of  V. cholerae.

         non-O1, non-O139 V. cholerae ( NAG ) : cholera toxin과 관계없는 enterotoxin을 분비. 

               : enterotoxine은 heat stable하고 Y. enterocolitica가 생산하는 heat stable enterotoxin과 관계있다.

        jejunal disaccharidase ( including lactase ) 의 activity impairment는 보이나 glucose absorption은

        usually preserved.

Clinical manifestation

        incubation period : 6hr-5days ( average 2-3 days )

        watery diarrhea, vomiting

        low grade fever

        in severe cases

          - profuse, painless, watery diarrhea ( " rice water consistency " ) with fishy odor

            때때로 mucous도 있지만 no blood.

          - fluid, electrolyte loss ---> thirst, tarchycardia.

          - tarchypnea, irritability, sunken ant. fontanele, poor skin turgor, circulatory collapse, stupor

           ---> if, untrated ---> Renal failure.

         diarrhea는 massive 하고 onset 24hr내에 vascular collapse가 일어나며 fluid loss는 1wk이상 지속된다.

Complications

    ; lethalgy, seizure, altered consciousness, fever, hypoglycemia, death

    ; inadequate fluid, electrolyte replacement

           --> ATN

           --> ARF

  ; potassium depletion, acidosis, hypokalemic arrhythmia

           --> sudden death.

  ; low potassium levels

           --> paralytic ileus, abdorminal distension

    ; 10% 이상에서 prolonged drowsiness, coma, seizure attacks.

    ; ♥seizure associated with hypoglycemia

           --> coma, death

           - hypoglysemia (+) ; 14.3 % death.

       - hypoglycemia (-) ; 0.7 % death

  ; pulmonary edema due to fluid overload

    ; transient tetani due to electrolyte inbalance

Diagnosis

       two selective media : TCBS, TTGA

       polyclonal-, monoclonal-based antibody test

       : direct detection of V. cholerae O1 in stool

       various enzyme- linkd immunosorbent assay : toxin detection

       DNA method ( probes, PCR ) : rapid diagnostic stool

       serologic assay : illness onset 7-14days후

                       vibriocidal, agglutinating, toxin neutralizing Ab의 reterospective detection

Treatment

      fluid, electrolytes replacement.

        WHO-ORS ( 1 L에 Na 90 mmol, K 20 mmol, Cl 80 mmol, glucose 111 mmol, bicarbonate 30 mmol )

             new oral solution ( rice based ORS ) : superior to WHO-ORS

         : oral hydration은 child가 obtunded, ileus, shock이 없는 한 treatment of choice.

         : vomiting 은 oral rehydration의 Cix이 아니다.

         : food 은 될 수 있는되로 빨리 restriction해야하고 refeeding은 purging                      

           rates &  diarrhea의 duration에  영향을 미치지 못 한다.

      Antibiotics : illness의 duration을 shortening시킨다.

                 resistance가 common

          i) Trimethoprim-sulfamethoxazole : 10mg/kg/24hr TMX & 50mg/kg/24hr SMX  #2 X 3days

          ii) older children : Tetracycline 50 mg/kg/24hr # 4 X 2-3 days

      다른 antidiarrheal compunds : not appropriate.

Prevention

      most practical method , in infants : prolonged breast feeding

      safe food and water, profer handring of swage : long term sol. to the problem

      Vaccination : high priority

               현제 사용 중인 vaccines 은 killed organism을 IV, 6 month마다 booster.

               vaccination 3-6 month에 50 % efficacy

               : vaccine의 low efficacy & high reaction ( pain, erythma, local indulation, fever, hardness ) 때문에 

                 exposure의 probability가 높은 very high risk host에만 사용

               : 6 month 이하에서는 Rec. 안됨.

 

      most promising new vaccines.

          i) three dose, oral, killed whole cell with B subunit vaccine.

          ii) single oral dose of CVD 103-HgR ( Vibriocidal Ab. )

Chapter 186. Camphylobacter

Etiology

# pathogenic for human

    ; 8 species

  ; C. jejuni, C. fetus, C. hypointestinalis, C. coli, C. laridis, C. cinaedi, C. tennelliae, C. upsaliensis

★Table 186-1

   3. Campylobacter organism

        - thin Gram (-) rode

        - motile with flagellum

        - small(0.5-1mm), sl.raised smooth colonies

        - microaerophilic

        - oxidized(-), ferment carbohydrate(-)

Epidemiology

     : most frequent causes of bacterial gastroenteritis

   1. developed country --> more frequent than salmonella or shigella

   2. summer and fall, rainy season

   3. age distribution

       - bimodal --> 4세이하

                           adolescent & young infant

       - highest incidence --> 1세이하

Patholgy

   1. terminal ileum & colon --> inflammatory diarrhea

   2. microscopy

        ① acute inflammatory infiltrate

        ② swelling of lamina propria

        ③ crypt abscess

Pathogenesis

   1. mucosal invasion

       : mediated by bacterial surf. protein

   2. cytotoxin

       : mammalian cell damage

         promote invasion

   3. enterotoxin

       : C. jejuni --> chorera-like enterotoxin

      cf) C. fetus

             - 현저한 intestinal mucosa damage 없이 통과

             - surf. protein capsule --> inhibits opsonophagocytosis

Clinical Manifestation

    # severity

        ① species                             ------+ 에 의존

        ② host factor : age, immunosuppression등 ---+

Acute Gastroenteritis

         1. C jejui (90%-95%)

                 C. coli, C laridis --> 1-5%

               - IP 1-7 day

               - loose, watery or blood & mucus stool

               - fever, vomiting, malaise & myalgia

               - abd. pain

         2. mild infection --> 1-2day지속, viral gastroenteritis와 유사

         3. persistent or recurrent C. gastroenteritis

                 and emergence of EM resistence

                --> hypogammaglobulinemia, AIDS

         4. fecal shedding of untreated patients --> 적어도 2-3주

Bacteremia

    ; bacteremia without localized infection

           - ▲common systemic infection

    ; *C. fetus - more common

    ; Clinical Manifestation

           - fever, headache, malaise, night sweating, chill, weight loss, lethalgy

    - specific neurologic Sg (-)

    - abd. pain

Focal Extraintestinal Infection

         1. C. jejuni

               - meningitis, pancreatitis. cholecystitis, UTI, arthritis

               - in neonate or immunocompromised pt.

         2. C. fetus

               - endocarditis, pericarditis, thromboplebitis, mycotic aneurysm

               - meningitis, septic arthritis, UTI, lung abscess, cholangitis

Perinatal Infection

         1. C. fetus

         2. maternal C fetus & C jejuni

               --> aSx. abortion, stillbirth, premature delivery

                    neonatal inf. with sepsis, meningitis

         3. newborn inf with C jejuni --> diarrhea

Complication

    ; ★Guillain-Barre Syndrome

       - *1-3wks after C. jejuni gastroenteritis

       - G-B synd.

                   / more than 25% stool culture (+)

                   / 20- 40% serologic positive

       - ★Ab against gangliosides (GM1 & GD1b)

                   --> *demyelination

    ; reactive arthritis

       - adolescent & adult

       - 5-40 day after diarrhea

       - large joint, migrating, afebrile

       - synovial fluid : sterile

    ; IgA nephropathy & immune complex GN

    ; hemolytic anemia & rectal bleeding

Diagnosis

     1. culture

     2. rapid Dx.

         - direct carbofuchsin stain

         - indirect fluroscence antibody test

         - dark field microscopy

         - latex agglutination

     3. PCR

     4. ELISA

Treatment

     1. Gastroenteritis

         ① EM (50mg/kg/24hr) #4 5day

              - early Tx. --> Sx. duration & shedding 감소

              - late Tx. (4일이후)

                  --> shedding 감소, clinical improve (-)

         ② TC (> 7yrs)

         ③ ciprofloxacin (>17yrs)

         ④ furazolidone

     2. C. bacteremia or extraintestinal inf.

           : C. fetus --> Gentamycin

            EM에 resistent

Chapter 187. Helicobacter

  - TMC cause of acute & chronic antral gastritis

  - associated with peptic ulcer, gastric ca., lymphoma

Etiology

     1. G(-), S-shaped, spiral with small coated & multiple sheath

        unipolar flagella

     2. Campylobacter와 다른점

         ① unique fatty acid composition

         ② 16S ribosomal RNA sequence

         ③ ultrastructural characteristics

         ④ high urease production --> 진단적 가치

Epidemiology  

     1. factors associated with increased risk

         ① unsanitary & overcrowed living condition

         ② lack of running water

         ③ showing a bed

    2. developing country

          : 10yr --> half of all,  adult --> 80% 이상

    3. developed country

          : child --> unknown,  adult --> 40%

    4. no animal or environmental reservoir

Pathology & Pathogenesis

    1. H. pylori

         - high host & tissue specific

         - gastric epithelial epi. of antrum을 overlying하는 mucosal layer

         - not invade the gastric mucosa

         - intestine내의 gastric metaplasia에도 존재

 

    2. virulence factor

         ① urease-mediated ammonia production --> acidic pH중화

         ② spiral morphology & flagella

               --> mucosal layer penetrate

                    peristalsis에 저항

         ③ adhesion

         ④ cytotoxin & mediators of inflammation

    3. histopathologic hallmark of H. pylori

           --> chronic inflammation

         - adult : neutrophil & lymphocye infiltrate

         - children : lymphocytic --> lymphonodular hyperplasia

Clinical Menifestation  

       - 보통 clinically silent

    1. acute infection with H. pylori

       - aSx.

    2. chronic gastritis

       - more common menifestation

       - aSx.

       - endoscopic finding

            gross --> normal finding

            microscopic --> nodular antritis with hyperemia

    3. peptic ulcer ds.

        - gastric ulcer : adult -->80%  child -->unclear

        - duodenal ulcer -->90%-100%

        - H. pylori

             제거시 : duodenal ulcer recurrence --> 0-27%

             제거(-) --> 67-95%

    4. chronic inf. with H. pylori

        - 15% --> peptic ulcer

          1-2% --> gastric Ca

Diagnosis  

# invasive method

    ; flexible endoscopy to biopsy

           - *culture of biopsied tissue --> 90% growth

         - histopathology

         - *rapid urease test

# non-invasive tests

    ; ★PCR

  ; serology

       - no diagnostic

    - F/U the response to antimicrobial Tx.

                   / if eradication, negative or low level within 6mo

    ; ★urea breath test

           - *97% sensitivity, 100% specificity

Treatment  

# indication

  ; symptomatic gastritis or duodenal ulcer

# H2-blocker

    ; less effective in achieving long-term remission

# ★Triple Tx

  ; *bismuth & ampicillin (or TC) 4-6wk + metronidazole 3-4wk

# dual Tx.

  ; bismuth + amoxicillin 6wk

Chapter 188. Yersinia

(구판과 차례변경)

    # pathogen

        ① Y. pestis

        ② Y. enterocolitica

        ③ Y. psudotuberculosis

188.1 Yersinia Enterocolitica

Epidemiology

    ; primarily in children and young adults

           - mostly under 7yr

    ; cold months

    ; M>F

  ; I.P 1-11day

    ; ★Transmission

           - contaminated food or water

           - person-to-person spread

           - transfusioin-related disease from red blood cell-containing products

Pathology & Pathogenesis

   1. Pathogenesis

       - adhesion, toxin (enterotoxin, cytotoxin), invasion

   2. Pathology

       --> classic enteric pathology

   3. transfusion-related ds.

      ① pathogenic strain

           - iron필요

           - RBC containing product내에서만 존재

      ② 2주 이상 저장된 blood

           --> transfusion associated ds.의 risk 증가

Clinical Menifestation

    1. Sx. & Sg.

         - fever

         - abdominal pain (colicky)

         - diarrhea ( watery or mucoid with fecal leukocytes)

 

    2. 3Mo이하 : 20-30%에서 bacteremia

 

    3. complication

         : uncommon in children

       ① erythema nodosum

       ② hemolytic anemia

       ③ thrombocytopenia

       ④ bacteremia spread to other site

           : meningitis, hepatic abscess, pneumonia

       ⑤ Yersinia triggered reactive arthritis

            - most frequent Cx.

            - extrimities

            - synovial fluid내 organism (-)

Diagnosis

    1. history

    2. stool exam : leukocytes   

# culture

    ; *▲useful diagnostic tests

# serology

Differential Diagnosis

    ; *shigella, enteroinvasive E coli

  ; mesenteric adenitis due to Y. pseudotuberculosis

    ; inflammatory bowel ds.

  ; reactive arthritis due to other cause

Treatment

    1. aminogycoside + 3rd generation cephalosporin or fluoroquidone

    2. rifampin,

      bactrim

    cf) amoxicillin --> Tx. failure

188.2 Y. Pseudotuberculosis

= psudoappendicitis syndrome without diarrhea

Pathogenesis

Pathology

① ileal & colonic mucosal ulceration

        ② mesenteric adenitis

        ③ necrotizing, epithelioid granuloma of mesenteric node

             --> DDx. with Y. enterocolitica

        ④ appendix --> gross but microscopically normal

       # Y. pseudotuberculosis Ag.

            - bind directly to HLA class 2 molecules

            --> function as superantigen

            --> clinical synd. resembling Kawasaki ds.

Clinical Manifestation

    ; fever, abdominal pain(diffuse or RLQ)

    ; tenderness over the McBurny point

           - strong clinical suspicion of appendicitis

    ; at surgery

           - *thickened, shiny terminal ileum

           - *enlarged necrotic mesenteric LN

Diagnosis

# ★Abdominal U/S

    ; characteristic picture of enlarged mesenteric LN

    ; thickening terminal ileum

    ; no image of appendix

# culture

    ; ★mesenteric LN culture

           - *▲good

    ; *never isolated from stool

Differential Diagnosis

     ① appendicitis

     ② inflammatory bowel ds.

     ③ non-specific intra abd. inf.

Treatment

 Y enterocolitica와 동일

188.3 Y. Pestis (= Plaque)

Epidermiology

    ; *transmitted by the bite of fleas

    ; endemic in wild rodent population of the western and southwestern US

Clinical Menifestation

# IP

    ; bulbonic plaque : 2-6day

  ; pneumonic plaque : 1-72hr

Prevention

# primary prevention

    ; avoidance

# *Killed Whole-Cell Vaccine

    ; ★Indication

           - laboratory and field personnel working directly with the organism

           - person engaged in aerosol esperiments

           - person engaged in field operation where enzootic plaque is known and preventing exposure to rodents and fleas is not possible

    ; *not recommended for routine immunization

Treatment

# *SM 30mg/kg/day im #2 for 10days

# septicemia, meningitis

    ; iv CM 100mg/kg/24hr divided every 6hr

# mild disease older than 10yr

    ; oral CM or TC

# contact with pulmonary plaque

  ; TC or bactrime

Prognosis

      # mortality

           - untreated bulbonic plaque --> 60-90%

           - untreated pulmonary plaque --> 100%

           - early treated bulbonic plaque --> 10%이하

Chapter 189. Tularemia

; more commonly in second decades

# classification

  ① *ulceroglandular (60-80%)

  ② typhoidal (5-15%)

  ③ glandular (10-15%)

  ④ oropharyngeal (5-10%)

  ⑤ oculogladular (1%)

Etiology

    ; *Francisella tularensis

Epidemiology

    ; ★Transmission Mode

       - direct contact with infected animal

    - through the bite of infected tick

    - inhalation of dust from contaminated environments

    - consumption of contaminated water            

    ; ★principle resorviors

           - *rabbits and ticks

    ; no person to person transmissin

Clnical menifestation

    1. IP : 3-5day

    2. Sx.

        - acute onset

        - myalgia, arthralgia, fever/chill (40-41℃)

        - headache, photophobia

    3. Ulceroglandular form

        - primary maculopapular lesion (72hr내)

        - painful ulceratiom (4-5day)

        - regional lynphadenopathy without lympangitis

        - generalized lymphadenopathy, splenomegaly

    4. Oropharyngeal form

        - purulent tonsilitis & pharyngitis

        - ulcerative stomatitis

    5. Glandular form

        - no local lesion

    6. Oculoglandular f4orm

        - paiful conjunctivitis with preauricular or cervical lymphadenitis

Diagnosis

# serum agglutination tests

    ; *▲useful diagnostic test

Treatment

# *SM 30mg/kg/day im #2 for 7-14days

    ; Tx of choice

# TC, CM

    ; effective, relapse are common

                 old children

                 14day

# GM

Prognosis

    1. fetality rate of ulceroglandular form : 2-5%

    2. pneumonia 동반 :30%

    3. second attack : occure but mild       

Chapter 190. Brucellosis

Etiology

# 4 species of pathogen

  ; *B. melitensis (goats & sheep)

  ; *B. abortus (cattle)

  ; B. suis (swine)

  ; B canis (dog)

# organism

    ; G(-) bacilli

    ; small, aerobic, nonspore forming, non-motile

  ; smooth (S) colony varients ==> more virulent

            rough (R) colony varient

Epidemiology

        - direct contact with sick animals

        - human to human transmission --> rare

Pathogenesis & Pathology

    1. facultative, intracellular parasites

    2. elaborating specific antibody

         --> agglutinin, opsonin, precipitin, complement fixation antibodies

    3. granuloma 형성 --> liver, spleen, LN, bone marrow

Clinical menifestation

    ; fever, arthralgia, malaise, weakness, CNS menifestation(esp. depression)

           - *▲common

    ; hepatosplenomegaly (30-40%)

  ; osteomyelitis, myocardits, endocarditis, genitourinary tract infection

Diagnosis

# isolation of organism

    ; culture

           - blood(75%), bone marrow(90%)

           - *use common commercial blood culture with venting & added CO2

           - *lysis-centrifugation method

                   / improvement of isolation due to intracellular organism

    ; *require as long as 4wks

# Brucella standard tube agglutination test

    ; ★Successful Treatment

           - ★rapid decline in IgG Ab but IgM Ab persist for months or yearys

# enzyme immunoassay based test

Treatment

# *TC in combination therapy

    ; Tx of choice

    ; TC (30-40mg/kg/day #4 po) or doxycycline(5mg/kg/day #2 po)

           with SM (30mg/kg/day #2 im) or GM(5mg/kg/day #2 iv)

# trimethoprim-sulfamethoxazole ( 10-12mg/kg of tremethoprim) + rifampin (15-20mg/kg)

Prognosis

    1. mortality rate : untrated --> 3%

    2. recovery : 6주이상 걸릴수도 있다.

Chapter 191. Listeriosis

Etiology

    ; *L. monocytogens

           - facultative anaerobic, nonspore-forming motile G(+) bacilli

Epidemiology

# epidemic human listeriosis

    ; foodborne transmission in several large outbreaks

# *nosocomial person-to-person transmission in Nursery & obsteteric situs

# sporadic endemic listeriosis

    ; foodborne, zoonotic spread, person-to-person transmission

Pathogenesis

# multisystem ds.

    ; *esp. pyogenic meningitis

    ; granulomatous reaction microabscess (liver, lung, kidney, adrenal, CNS, placenta)

# T cell mediated activation of monocytes by lympokines

          --> clearance of infection

Clinical menifestation

Listeriosis In Pregnancy

# early gestational Listeriosis

  ; spontaneoy abortion

# 2nd or 3rd trimester listerosis

    ; maternal flulike illness

    ; not infected fetus

# ★placental Listeriosis

    ; *premature labor and delibery

    ; maybe stillbirth

    ; ★infected premature fetus

           - *50-90% mortality

           - *disseminated disease at birth with diffuse pustular rash

Neonatal Listeriosis

★Table 191-1

    ; *resembling group B streptococci infection

# early onset (<5days, within 1-2day)

  ; septicemic form

  ; transplacental or ascending infection from the female genital tract

    ; *strong asso. with prematurity, obstetrical complications, recovery of L. monocytogens from maternal genital tracts, sepsis without CNS localization

    ; mortality 30%

# late onset (>5days, mean 14day before 30days)

    ; *term infants

    ; mother - asymptomatic, negative culture

  ; *purulent meningitic form

    ; mortality < 20%

Postnatal Infection

    ; *▲often seen associated with underlying malignancy and/or immunosuppression

    ; Clinical Manifestation

           - meningitis

    - non-meningitic diffuse or localized CNS inf.

Diagnosis

# culture of L. monocytogens

    ; blood, CSF in newborn

    ; maternal cervix, vagina, lochia, placenta

# *serodiagnositic tests have not proved useful

Treatment

         ① ampicillin

         ② GM + ampicillin

         ③ vancomycin or vancomycin+ampicillin

       # duration : 2wks ,

             immunosuppressive pt. --> 3-6wks

       # cepalosporin계 --> not suitable

Prognosis

       ① premature infant의 50%이상

       ② early onset neonatal sepsis의 30%

       ③ late onset neonatal meningitis의 15%

Chapter 192. Botulism

Definition

    ; acute, flaccid paralytic illness caused by neurotoxin produced by C. botulinum, C. butyricum, C. baratii

# ★3 form

    ; *infant botulism - ▲common

  ; food borne (classic) botulism

  ; wound botulism

Etiologic Agents

   1. B. toxin

     1) most poisonous substance known

    ^신2) parenteral human lethal dose

         : 10^-7mg/kg

     3) block neuromuscular transmission

        -> death through airway & resp. muscle paralysis

    ^신4) 7 antigenic toxin type : A-G

          a. neurotoxigenic C. butyrium : type E-like toxin

                 "         C. baratii   : type F-like toxin

          b. toxin type A, B, E, F

                  : cause of human botulism

                 type C, D : other animal

                 type G   : not established

      5) simple di-chain protein 

                 100KD heavy chain

                 50KD light chain

# C. botulinum

  ; G(+), spore-forming obligate anaerobic

    ; spores survive boiling for several hours

    ; botulinum toxin is heat labile & destroyed by heating at 80℃

Pathogenesis

  ^신1. all 3 form of botulism

       : final common pathway 통해 ds. produce

      # toxin

         : blood stream 에 의해 peripheral cholinergic synapses

           -> irreversible bind

           -> acethylcholine release를 block

           -> impaired autonomic & neuromuscular transmission

   2. infant botulism

       : spore of C. strain 의 ingestion

         -> spore germination, multiplication & production of B. toxin in the large intestine

         -> infectious ds.

   3. foodborne B.

       : preformed B. toxin이 있는 음식물을 먹음으로서 생기는 intoxication

   4. wound B.

       : C. botulinum에 의해 traumatized tissue의 spore germination & colonization

Epidemiology

   1. infant botulism

     1) most striking epidemiologic feature

         : age distribution

           - case의 95% : 3wk-6Mo(peak 2-4Mo)

                        -> sudden infant death syndrome과 match

                           but 6일이내 or 363일 이상의 age에서도 reported

     2) M:F = 1:1

        all major racial & ethmic groups에서 occured

     3) 주로 type A, B strain 에 의해

     4) identified risk factor

          . ingestion of honey

          . slow intestinal transit time(less than 1 stool/day)

       # breast feeding

          : protection against fulminant, sudden death

  2. foodborne B.

     1) most preserved foods

         : low-acid(PH 6.0 이상) home-canned foods

     2) 주로 temperate zones

     3) type A, B(TMC)

        (Alaska : type E)

  3. wound B.

      : rare

        but young, physically active male(trauma risk증가) 에 잘 발생

      : drug abuser - 증가

Pathology

  1. B. toxin

     - physiologic, not cytotoxic poison

     - no overt macroscopic or microscopic pathology

        but secondary change(autopsy에서)

          : pneumonia, petechia on intrathoracic organ

     - diagnostic technique : no

  2. healing process

    ; sprouting of new terminal unmyelinated motoneurons

Clinical Manifestation

1. B. toxin

    1) blood flow & density of innervation

        -> greatest in the bulbar musculature

        ∴ all 3 form

             : neurologically as a symmetrical, descending flaccid paralysis of the cranial n. musculature

    2) bulbar palsy(-)

        -> not botulism

           but infant : poor feeding, weak suck, feeble cry, drooling, and obstructive apnea

       # bulbar palsy나타나기 전에 generalized weakness & hypotonia가 먼저 나타날 수 있다

  2. in older children with foodborne or wound botulism

    1) neurologic sx

        : diplopia, blurred vision, ptosis, dry mouth, dysphagia, dysphonia & dysarthria,

          gag & corneal reflexes감소

    2) toxin : only act on motor nerves

        ∴ paresthesia

               : hyperventilates from anxiety 외에는 botulism시 not seen

    3) sensorium : clear, but slurrred speech 로 인해 확인하기 힘들다

 

  3. foodborne botulism

    1) begin with G-I Sx

         : N/V & diarrhea (case 1/3)

    2) flaccid paralysis  나타나면 constipation이  mc Sx

    3) IP : 18-36hr (range : 2hr-8days)

        cf. wound B.의 IP : 4-14days

    4) fever : 2ndry inf. (pneumonia) 없으면 no

             cf. wound B. : fever(+)

      # all 3 form

         : wide spectrum in clinical severity

         . mild with minimal ptosis, flattened facial expression, minor dysphagia &  dysphonia

         . fulminant with rapid onset of extensive paralysis, resp. distress, & frank apnea

      # clinical hallmark of botulism

          : fatigability with repetitive m. activity

  4. infant botulism

      1) 1st indication of illness

          : constipation(3일 이상 no defecation)

      2) lethargy, listlessness, poor appetitie, weak cry & diminished spontaneous movement

      3) dysphagia

          : evident as secretion drooling from mouth

      4) paralysis advance

          -> gag, suck & corneal reflex 감소

      5) oculomotor palsy (+)

         pupillary light reflex : unaffected until severe paralysed

                               or initial sluggish

      6) loss of head control

          : typically prominant sg.

      7) resp. arrest

          : unswallowed secretion or obstructive flaccid pharyngeal musculature

            에 의해 airway occlusion

          : infant을 lumbar puncture position 후 resp. arrest occure

Diagnosis & Differential Diagnosis

    1. classic feature of botulism

      : acute onset of flaccid descending paralysis with clear sensorium,

        no fever, & no paresthesia

   ^신2. table 192-1

      : DDx of foodborne & wound B.

    3. routine lab studies

      1) CSF finding

          : dehydration or starvation ketosis 없으면 normal

      2) EMG

          : defect in neuromuscular transmission

          a. foodborne & wound B.

             : facilitation(potentiation) of the evoked muscle action potential

               at high frequency (50Hz) stimulation

          b. infant B.

             : acronym BSAP

               - brief, small, abundant motor-unit action potentials in clinically weak muscles

    4. DDx of foodborne & wound B.

       1) myathenia gravis

           . edrophonium (Tensilon) test

           . specific antidote : PAM

       2) G-B synd.

           . lumbar puncture

              : CSF protein conc.증가

           . EMG

              : onset 후 4-6wks 후 n. conduction velocity 가 slow

     5. infant botulism

       1) most common admission Dx

           : rule-out sepsis

       2) DDx : table 192-2 ^신

       3) 6Mo이하의 previously healthy infant에서 constipation Hx 있으면서

          weakness with difficulty in sucking, swallowing, crying or breathing이

          acutly develope될때  infant botulism suspect

     6. Dx of botulism

        . serum 에서 B. toxin 의 존재를 demonstration

        . wound material or feces 에서 B. toxin or organism 을 demonstration

Treatment

   ^신1. 3 principles

        a. fatiguablity with repetitive activity

            : clinical hallmark

        b. Cx이 올 수 있으므로 피하는 것이 좋다

        c. meticulous supportive care가 필요

 

 

   ^신2. 1st principle

        : feeding & breathing 에 적용됨

 

       1) correct position

          - to protect airway & improve resp. mechanics

          a. pt : placed face up on a rigid-bottomed crib( or bed)

                head -tilted at 30 degrees

            -> small cloth roll은 cervical vertebra 아래두고 head을 뒤로 tilt시킴

            -> secretion drain to the post. pharynx & away from the airway

            -> abd. viscera pull the diaphragm down

            -> improve resp. mechanics

          b. pt's head : should not be elevated by bending the middle of the bed

                      ∵ hypotonic thorax -> slump into the abdomen

                                          -> compromised breathing

 

       2) endotracheal intubation

          a. airway potency 유지와 aspiration 피하기 위해 propylactic하게 사용

          b. PCO2 증가

              : alveolar hypoventilation & irreversible m. fatigue 의미

          c. 입원 환자의 약 1/2이 intubation 필요

          d. tracheostomy : almost never required

              global faccid paralysis pt 에서 proper positioning

              -> permanent sequelae 없이 수 주 or 수 개월 동안 intubation에 tolerable

       3) feeding

          a. sufficient oropharyngeal strength & coordination으로 breast or bottle

             feeding 할 수 있을때까지 nasogastric or nasojejunal tube keep

          b. expressed breast milk

             : most desirable food

               - immunologic component (IgA, lactoferrin, leukocyte)

          c. tube feeding

            - restoration of peristalsis

            - nonspecific but essential part of eliminating C. botulinum from the intestinal flora

          d. intravenous feeding (hyperelementation)

             : potential of inf. & advantage of tube feeding

              -> discouraged

 

     3. antibiotics

        a. secondary inf. 에 사용

            : trimethoprim-sulfamethoxazole, nalidixic acid

              but aminoglycoside

               -> neuromuscular junction에서 B. toxin의 blocking action을 증가시킴

        b. uncomplicate infant or foodborne botulism에는 사용하지 않는다

        c. wound botulism

            : Abc and antitoxin

     4. antitoxin

        a. horse-serum-derived product

        b. side effect

            - serum sickness

            - anaphylaxis

            - potential lifelong sensitization to equine protein

 

  ^신 5. a. sensation은 intact하므로 auditory, tactile & visual stimuli 시키는 것이 효과적

       b. maintaining strong central resp. drive is essential

            ∴ sedative or CNS depressant : CIx

       c. full hydration & stool softness

          : protracted constipation감소

          (cathartics : not recommend)

       d. B. toxin & organism : 3주 동안 feces로 excretion되므로 주의 요함

       e. bladder atony

          : head을 support 하면서 sitting position으로 gentle suprapubic pressure 가함

           -> complete voiding & UTI risk 감소

Complications

 ^신 table 192-3

Prognosis

   # case fatality ratio

       . hospitalized infant botulism

          : <1%

       . foodborne & wound botulism

          : varies by age( younger pt : best px)

   # hospital stay

       infant botulism : average 1Mo

                 type B toxin : 3.7wk

                 type A toxin : 5-6wks

Prevention

   1. foodborne botulism

     . adhering to safe method of home canning

        (pressure cooker & acidification)

     . avoiding suspicious foods

     . heating all home-canned foods (80도 for at least 5min)

   2. wound botulism

     . thorough cleansing & surgical debridement of contaminated traumatic injuries with appropriate Abc

     . not abusing illicit drugs

   3. infant botulism

     . inhale and then swallow airborne clostridial spores

        -> unpreventable

     . honey - source of botulinum spore

             - 1세 이하에서는 unsafe food

     . breast feeding

         - slow the onset of infant botulism

         - the risk of resp. arrest 감소

Chapter 193. Tetanus(=lockjaw)

Definition

; *acute, spastic paralytic illness caused by tetanospasmin, neurotoxin produced by C. tetani

Etiologic Agent

   1. C. tetani

     . motile, G(+), spore-forming obligate anaerobe

     . not tissue-invasive organism

   2. toxin  : tetanospasmin

               - 2nd most poisonous substance known

               - lethal dose : 10-6mg/kg

Epidemiology

# *▲common form

    ; neonatal (umbilical ) tetanus

   2. 대부분 60세 이상에서 occure

      but toddler-aged & neonate 때도 occur

Pathogenesis

   1. T. toxin

     . 150KD simple protein (100KD heavy chain & 50KD light chain)

     . bind at the neuromuscular junction

      -> cytoplasma of alpha-motoneuron 으로 retrograde axonal transfort

      -> endocytosed by the motor n.

         (sciatic n.에서 transfort rate는 3-4mm/hr)

      -> toxin은 spinal cord내의 motoneuron에서 나와 인접 spinal inhibitory internueron           

         으로 들어가 neurotransmitter release을 prevent

      -> voluntary coordinated movement을 하는 normal inhibitory of antagonistic m.을 block

      -> affected m.은 maximal contraction

    # autonomic nervous system

      : unstable in tetanus

Clinical Manisfestation

    1. IP : 2-4day (injury 후 수개월도 가능)

    2. clinical form  . localized

                    . generalized(mc)

                    . cephalic

    3. generalized tetanus

      1) trismus(masseter m. spasm or lockjaw)

          : case의 1/2에서 presenting sx

      2) early sx

         : headache, restlessness, & irritability

           -> stiffness, difficulty chewing, dysphagia, & neck m. spasm

 

      3) sardonic smile of tetanus (risus sardonicus)

         : intractable spasm of facial & buccal m.

      4) paralysis 가 abdominal, lumbar, hip & thigh m.로 extend

         -> arched posture, opisthotonus

 

      5) laryngeal & resp. m. spasm

         -> airway obstruction & asphyxiation

      6) T. toxin : not affect sensory n. or cortical function

         -> conscious, extreme pain, fearful anticipation of next tetanic seizure

 

      7) seizure

          . sudden, severe tonic contraction of the m., with fist clenching, flexion,

            & adduction of the arm and hyperextension of the leg

          . Tx 하지 않은 경우 수초에서 수분 지속

      8) smallest disturbance by sight, sound or touch

         -> tetanic spasm 유발

      9) bladder sphincter spasm

         -> dysuria, & urinary retention

     10) fever : 40도

              : spastic m.에 의해 substantial metabolic energy 소모되어 fever(+)

 

     11) autonomic effect

         : tachycardia, arrythmia, labile hypertension, diaphoresis,

          cutaneous vasoconstriction

     12) tetanic paralysis

           onset 후 1wk : more severe

                    2wk : stabilize

                    1-4wk : 점차 회복

 

     13) neonatal tetanus (tetanus neonatrum)

          . infantile form of generalized tetanus

          . 출생후 3-12일 이내에 manifest

             : progressive difficulty in feeding (ie,sucking & swallowing)

                with associated hunger & crying

          . 특징 - paralysis or diminished movement

                - stiffness to the touch

                - spasm with or without opisthotonus

          . umbilical stump

             : remnants of dirt, dung, clottted blood or serum

   4. localized tetanus

      : painful spasm of the m. adjacent to the wound site

        -> generalized tetanus로 진행될수 도 있다

   5. cephalic tetanus

      . rare form of localized tetanus involving the bulbar musculature

      . occur with wound or foreign body in the head, nostril or face

      . chronic otitis media와 잘 동반

      . 특징 - retracted eyelid    

             - deviated gage

             - trismus     

             - risus sardonicus

             - spastic paralysis of tongue & pharyngeal musculature

Diagnosis & Differential Diagnosis

    1. Dx : 임상적으로 진단

      1) typical setting

           unimmunized pt

               - 2주 이내에 injury or born

               - with trismus, other rigid muscles, & clear sensorium

      2) regular lab : normal

          . peripheral leukocytosis

             - 2ndary bacterial inf.

             - tetanic spasm의 지속으로 인한 stress때문

          . CSF : normal

                 but intense m. contraction으로 pr. 증가 할 수 있다

          . EEG & EMG : normal

          . G stain : C. tetani not always visible

                     1/3에서 isolation(+)

 

    2. DDx

       1) fully developed, generalized tetanus

           : other ds.와 잘 구별된다

             but trismus : parapharyngeal, retropharyngeal or dental abscess or 드물지만

                           brain stem을 involve 하는 acute encephalitis에 의해 생길수 있다

       2) rabies

           . trismus with seizure

           . 감별점 - hydrophobia, marked dysphagia, predominant clonic seizure

                      CSF pleocytosis

       3) strychnine poisoning : tonic m. spasm & generalized seizure activity

                               나타날 수 있지만 trismus는 (-) 그리고

                               tetanus와는 달리 spasm사이에 general relaxation나타난다

       4) tetany <-- hypocalcemia

           : laryngeal & carpopedal spasm (+) but trismus(-)

       5) epileptic seizure, narcotic withdrawal or other drug reaction

Treatment

# ★Principle Of Management

    ; eradication of C. tetani

    ; wound environment conductive to its anaerobic multiplication

  ; neutralization of all accessible tetanus toxin

  ; control of seizure  & respiration

  ; palliation & provision of meticulous supportive care

  ; prevention of recurrence

# surgical wound excision & debridement

# ★TIG

  ; *tetanus toxin이 spinal cord로 axonal ascent 된 후에는 TIG로 neutralized시키지 못하므로 그 전에 투여해야 함

    ; *500 U single IM (as high as 3,000-6,000 U recommend)

  ; intrathecal TIG : not effective

  ; TIG을 사용할 수 없는 경우

    - human intravenous immune globulin(4-90u/ml of TIG포함)

                   / dosage : not known

            / 장점 - longer half-life(30일)

            - allergic & serum sickness(-)

         - TAT

            / horse serum sensitivity check해야 하고 desensitization 필요

            / 5만-10만 U(1/2 : IM, 1/2 : IV) but 1만 U도 가능

       - 15%에서 serum sickness (+)

# antibiotics

  ; *PC G

        - AB of choice

    - *100,000 u/kg/24hr # 4-6 for 10-14day

    ; metronidazole

           - equally effective

  ; EM & TC

           - 9세 이상

# muscle relaxant for all pts

  ; diazepam

       . relaxation & seizure control

       . 0.1-0.2mg/kg every 3-6hr IV for 2-6wks  -> tapering

  ; baclofen

       : only ICU setting 에 이용

    ; magnesium sulfate, other benzodiazepine, chlorpromazine, dantrolene

# neuromuscular blocking agent

    1) best survival rate

    2) vecuronium, pancuronium

    3) produce general flaccid paralysis

      -> managed by mechanical ventilation

  9. autonomic instability

     : α-and β-blocking agent(esp.morphine)

  10. meticulous supportive care

    1) 조용하고 어두운 곳에 격리시킴

    2) minor stimuli에 의해서 tetanic spasms 유발 될 수 있기 때문에

       불필요한 sound, sight, touch등으로부터 protection 해 주어야 한다.

    3) endotracheal intubation

       tracheostomy kit

    4) cardioresp. monitoring, frequent suction

       maintanence of fluid, electrolyte & caloric needs

Complication

    1. aspiration of secretion & pneumonia

    2. endotracheal intubation & mechanical ventilation

      -> pneumothorax & mediastinal emphysema

    3. seizure

      -> . laceration of the mouth or tongue

          . intramuscular hematoma or rhabdomyolysis with myoglobulinuria & renal failure

          . long bone or spinal fracture

    4. venous thrombosis, pul. embolism, gastric ulceration c or s hemorrhage

       decubitus ulceration

    5. excessive use of m. relaxant

       -> iatrogenic apnea

    6. disorded autonomic n. system

       -> . cardiac arrhythmia(asystole, unstable blood pr.)

           . labile temperature regulation

Prognosis

    1. most important factor influencing outcome

      : quality of supportive care

    2. mortality

       a. highest in very young & very old

       b. 주로 1wk이내

       c. fatality rate

           . generalized tetanus : 5-35%

           . neonatal tetanus

                 intensive care(+) : < 10%

                      "       (+) : > 75%

           . cephalic tetanus

              : poor px(breathing & feeding difficulty)

     3. favorable Px

         . long IP

         . absence of fever

         . localized ds.

     4. unfavorable Px

         . injury 후 trismus onset 시기 : 1wk 이내

         . trismus 후 generalized tetanic spasm onset 시기 : 3일 이내

     5. sequele of hypoxic brain injury esp. infant

         . cerebral palsy

         . mental ability 감소

         . behavioral difficulty

Prevention

# *serum Ab level ≥ 0.01U/ml

    ; protective

# active immunization

  ; *DTP 2, 4, 6mo with a booster at 4-6yr

           and then at 10yr interval Td

      2) immunization of women with tetanus toxoid

         - prevent neonatal tetanus

         - 250 Lf unit , single dose 로 3rd trimester of preg.

            -> transplantal Ab : 적어도 4Mo까지 child protect

# unimmunized persons 7 or more yr old

    ; 3 dose of Td toxoid

        - 2nd : 1st후 4-6wk

    - 3rd : 2nd후 6-12Mo

# ㉿Tetanus Prophylaxis For Wound Infection

    ; dog or other animal bite

           - always tetanus toxoid

    ; all wounds

           - require human TIG

           - exception) fully immunized pt

    ; unknown or incomplete immunization Hx, crush, pnucture or projectile wound, wound contaminated with saliva, soil or feces, avulsion injuries, compound fracture, frostbite

           - 250 U of TIG IM

  ; ★highly tetanus-prone wound : undebridable with substantial bacterial contamination or > 24 hr old

           - *500 U of TIG IM

    ; tetanus toxoid

           - TIG 나 TAT와 동시에 투여해도 된다

       - *unknown or incomplete immunization status경우에는 어떤 wound 라도 투여한다

           - *clean & minor wound지만 last booster후 10년이 지난 경우에는 투여한다.

    - *more serious wound면서 last booster후 5년 지난 경우에는 투여한다.

# delayed wound care시 active immunization 바로 시작

# fluid tetanus toxoid 가 absorbed or precipitated toxoid보다 more rapid immune resposne 보이지만absorbed toxoid가 more durable titer를 가진다

Chapter 194. Anaerobic infections

Other Clostridial Infections

   - clostridium : G(+), anaerobic, spore-forming bacilli

   - infectious synd.

       bacteremia & intraabdominal, biliary, pulmonary, genital tract,

        CNS & soft tissue inf.(including gas gangrene)

Etiology

  . 60 species 이상

  . human pathogen

     - C. difficile : most commonly isolated

                  : Abc-associated colitis (pseudomembrane colitis)

                  : 주로 adult

     - C. tetani

     - C. perfringens : C. tetani 다음으로 most common pathogen

Pathogenesis

  1) C. perfringens

    - 전 세계적으로 soil과 대개 척추 동물과 사람의 intestine의 inhabit

    - 5 types (A-E) based upon the production of 4 lethal toxins

        α toxin : in all strain

                : major clostridial toxin and acts as phospholipase

        β toxin : strain B & C

                : transmural necrosis

        ε toxin : strain B & D

        ι toxin : strain E

     - other toxins : hemolysin and enzyme with collagenase, gelatinase, protease, 

                      hyaluronidase, DNase, neuraminidase activity   

  2) toxin production -> tissue damage -> systemic absorption

  3) local gas production : C. perfringens의 특징으로 이로 인해

                          crepitant cellulitis, emphysematous cholecystitis, gastritis, cystitis 생김

                          그 이외에도 E. coli, streptococus, anaerobics & aerobics의 mixed inf.에 의해서도

                          deep tissue의 gas 형성 할 수 있다

Infections

Gas Gangrene

     1) etiology     C. perfringens(80%)

                   C. septicum / C. novy / C. histolyticum / C. falax /C. bifermentans

     2) pathogenesis  

       . clostridium균에 의해서 contamination된 traumatic injury나 biliary or colonic resection 등의

         surgical wound뒤,

          -> toxin production

          -> edema, thrombosis, necrosis and local gas production

          -> septicemia, shock

       . vegetative form의 replication 및 toxin production 조절하는 local tissue factor

           : tissue hypoxia / foreign body / vascular insufficiency /

             necrotic tissue / co-infection with other bacteria

       . C. septicum : relative aerotolerant

                    : obvious tissue damage없이 GI tract로 부터 blood stream으로

                      spontaneous gas gangrene 유발한다

                      그러므로 primary GI tract disease or immune defect는

                      C. septicum gas gangrene의 predisposing factor이다

 

     3) clinical manifestation

       . incubation : 1-4days

       . fulminant inf. with local tissue inf. and systemic toxicity

       . wound site의 pain -> 1st Sx

           skin : pale, bronze color or hemolytic bullae, characteristic sweat odor with

                 brown serosanguineous discharge

           local sg

               : tense edema, tenderness,

                 & gas (+) --> X-ray or scan으로 알 수 있다

       . pale and loose contractile m.(no bleeding)

       . systemic Sx

     4) DDx

        cellulitis / streptococal fascitis / mixed aerobic-anaerobic necrotizing

        fascitis / synergistic gangrene due to S. aureus and anaerobic streptococi

     5) Tx

        . extensive surgical debridement & immediate Abc Tx

        . choice : PC 250,000 unit/kg/day IV #4

                  but 최근 animal study에서 clindamycin(40mg/kg)

                    -> PC, metronidazole, or  imipenem보다 more effective

        . supportive care

        . antitoxin : not available

     6) prognosis

        . overall mortality : 25%

        . poor Px : in presence of intravascular hemolysis, renal failure,

                   abdominal m. involvement, spontaneous gas gangrene

     7) prevention

        . early careful wound debridement

        . no effective active immunization

Bacteremia

       bacteremia without an obvious focus of inf.

          : C. perfringens, C. tetani, C. septicum

       C. septicum bacteremia associated with malignancy(leukemia, colon cancer) and

           neutropenia(chemotherapy, cyclic neutropenia)

Focal Infections

      . penetrating trauma of surgery of abdomen,

         -> intra-abdominal inf.(subdiaphragmatic abscess)

      . biliary tract inf. asso. with emphysematous cholecystitis, tubo-ovarian & pelvic abscess

      . septic abortion -> uterine gas gangrene

      . oropharyngeal aspiration후 -> empyema

      . penetrating trauma나 otitis, sinusitis후 -> cbr. abscess

      . soft tissue inf.

Enteric Infections

C. Perfringens Food Poisoning

        mild and common form of food poisoning

Enteritis necroticans - PIGBEL

     1) endotoxemia due to beta-toxin of C. perfringens type C

        in sheep, calves, piglets, malnourished humans

     2) clinical manifestations

       . segmental disease of small bowel with intervening of patches of

          hemorrhagic necrosis

       . incubation : 1-7 days(대개 2일)

       . abdominal pain and distension, emesis, bloody stool, pneumatosis,

          cystoides intestinalis

     3) Tx : PC G or clindamycin

             supportive care

AB Associated Colitis, Pseudomembraneous Colitis

      1) etiology ; toxin A & B of toxigenic C. difficile

            ^신 . toxin A(308000 D)

                 - intestinal mucosa에 작용

                 - diarrhea

            ^신 . toxin B(270,000D)

                 - low dose : vascular permeability 증가

 ,               - high dose : lethal to experimental animal

 

      2) predisposing factor

        . antibiotics Tx : 원인 항생제 : CM(most common) / penicillin /

                                     ampicillin / cephalosporin / amoxicillin / TC

                       : 기전 - by suppressing of other micro-organism

                                responsible for a normal process that prevents

                                the growth of the organisms

        . MTX and other chemotherapeutics / antiviral agents / diet change /

          intestinal motility disorder / uremia / anesthesia

        . asymptomatic colonized or activity infected patients와 접촉 있을 경우

 

      3) clinical manifestation

        . 대개 항생제 사용후 4-8일 후 시작하나, D/C하고 21일 뒤까지 연기되어

          나타날 수 있다

        . 항생제 사용기간이 중요한 것은 아니며, 대개 경구 복용시 나타나나,

          parenteral 사용시에도 나타날 수 있다

        . wide range of severity

          severe case : severe hemorrhagic colitis with protein losing

                       enteropathy / hypoalbuminemia / shock / fever /

                       toxic megacolon / shock and death

      4) diagnosis

        . detection of fecal toxin B(cytotoxin) in symptomatic pt

        . stool or blood culture에서 10⁴-10⁵ 균/gram

          selective media for culture CCFA

        . detection of toxin with ELISA or latex agglutination

        . colonoscopic findings(not necessary for all patients)

           - 특징적인 pseudomembranous nodules or plaque in rectum,

               sigmoid distal colon

      5) DDx

         . Staph. aureus associated enterocolitis

         . other infectious diarrhea

         . hemolytic uremic syndrome

         . irritable bowel syndrome

         . malabsorption syndrome

         . neutropenic colitis or cecitis in immune-suppressed patient

      6) treatment

         . 사용중인 항생제 중단

            - mild case는 이것만으로도 48hr 이내 improvement보이고

               7-10일만에 complete resolution되기도 함

         . oral use of Saccharomyces boulardii

            : chronic C. difficle diarrhea & relapse in infants and young children에 effect

         . 심한 경우는 antimicrobial Tx

            -> choice는 oral vancomycin(20-40mg/kg/day q 6hrs for 7-14days)

            : oral metronidazole도 effective 하지만 child에서 routine use는 아님

            : toxic megacolon이나 adynamic ileus로 경구 복용이 곤란한 경우는

               IV vancomycin + metronidazole

         . Ix of surgery

            : toxic megacolon / cecal perforation /

              for administration of vancomycin into GI tract via ileostomy

      7) prognosis

          대개 mild and self limit

           but, severe case는 mortality rate가 20-30%

          relapse : 10-20%

Anaerobic Infectious Other Than Clostridial

  1. anaerobic inf. 의심할 수 있는 경우

     1) PROM, amnionitis, obstetrical difficulty

     2) peritonitis or septicemia asso. with intestinal obstruction and perforation

        or with appendicitis

     3) inf.에 대한 host의 response에 장애가 있는 경우

     4) subcutaneous abscess and inf. of female genital tract

     5) orofacial inf.

     6) aspiration pn.

     7) chronic inf. in isolated mucous memb.

   2. anaerobic pleuropulmonic ds. may be initiated by

     1) aspiration

     2) preceding extrapulmonic anaerobic inf.

        (OM, pharyngitis, bacterial endocarditis, peritonitis)

     3) penetrating chest wound or open heart surgery

     4) systemic ds. that impairs host response to inf.

 # Table 194-1

   3. clinical manifestation

     1) periodontal inf.

     2) periapical abscess or anaerobic osteomyelitis of mandible

     3) vincent angina(trench mouth)

     4) norma

     5) Ludwig angina

     6) necrotizing pn., putrid empyema, lung abscess

     7) brain abscess, subdural empyema, septic thrombophlebitis

     8) purulent meningitis

     9) anaerobic bacteremia

     10) others

Diagnosis

   4. Dx of anaerobic inf.

     1) anaerobic inf.에 대한 awareness

     2) culture를 위한 적절한 specimen의 selection & collection

     3) 균을 배양해내는 적절한 media와 technique

★Table 194-2 Clues To Presumtive Diagnosis Of Anaerobic Infection

Treatment

# AB therapy

    ; *▲effective

    ; *< 2cm small abscess

           - only AB treatment : effecitive

    ; *metronidazole(except: Propionibacterium, Actinomyces), CM, imipenem, beta-lactamase antibiotics combined with a beta-lactamase inhibitor (ticarcillin & clavulanic acid, ampicillin & sulbactam)

           - always active

    ; *clindamycin(10-20% of B. fragilis and non C. perfringens clostridia are resistant), cefoxitin(10%of B. fragilis and some clostridia are resistant), anti-pseudomonas penicillins

           - usually active

    ; *penicillin (inactive all B. fragilis and some other Bacteroides or clostridia), vancomycin (active against G(+) anaerobes)

           - variable active

    ; aminoglycosides(GM, KM) : not effective

Chapter 195. Legionella

# Legionellosis

  ; legionenaires's dis. (Pn)

    ; invasive extrapulmonary infection

    ; acute flu-like illness known as Pontiac fever

Clinical Manifestation

# ★Legionnair’s Disease

    ; atypical pneumonia with extrapulmonary signs & symptoms

    ; *diarrhea, hyponatremia, hypophosphatemia, abnormal liver functions, confusions, renal dysfuntion

# Pontiac fever

    ; *high fever, myalgia, extreme debiltation, lasting for a few days

    ; develops following aerosol exposure

  2. a toxic or hypersensitivity response to Legionella

* Legionnaires's ds.의 attack rate: 0.5-5.0%

  Pontiac fever의 attack rate: 85-100%

Treatment

  1. EM, with or without rifampin

  2. newer macrolides (azithromycin, clarithromycin), fluoroquinolone agents (ciprofloxacin)

  3. duration of therapy for Legionnaires' ds: 2-3wk.

  4. alternative antibiotics

     : doxycycline & TMP-SMZ

Chapter 196. Mycoplasma Infections

Respiratory Mycoplasmas

 * mycoplasma pneumoniae

   : major cause of respiratory infection in school-aged children & young adults

Etiology

   : M. pneumoniae

Epidemiology

  1. Peak incidence of illness

   ① in school-aged children

   ② M. pneumonia가 children의 all Pn.중 5-9yr.에서는 33%, 9-15yr.에서는 70%차지

  2. incubation period: 1-3wk

Pathology, Immunology, & Pathogenesis

  1. nonspecific cold hemagglutinins reacting to the I antigen of RBC glycoproteins

     : the first antibodies detected

  2. cold hemagglutinins은 illness의 1-2주후기에 환자의 50%에서 적어도 titer가 1:32로 나타나고

     3주이후에는 4배이상 증가하여 6주에서 사라진다.

  3. cold hemagglutinin의 증가된 titer존재와 titer의 height는 illness의 severity와 비례한다.

  4. immunodeficiency states (hypogammaglobulinemia, sickle cell anemia)가진 환아에서는

     normal host보다 severe Mycoplasma pn.를 나타낸다.

     Mycoplasma pn.는 sickle cell pt에서 acute chest syndrome의 the most common infectious cause이다.

     AIDS환자에서는 not prevalent

Clinical Manifestation

# bronchopneumonia

  ; *▲common clinical syndrome

# onset of illness

    ; abrupt

# cough

  ; usually worsens during the 1st 2wk of illness, and then all symptom gradually resolve within 3-4wks

# pneumonia

  ; interstitial or bronchopneumonia

  ; the lower lobes

           - *▲common

    - *75% unilateral centrally dense infiltrates

    ; hilar lymphadenopathy - 33% of pt

    ; significant amounts of pleural fluid

# Laboratory Finding

    ; WBC count: usually normal

  ; ESR count: usually elevated

# M. pneumoniae

      : common inducer of wheezing in asthmatic children

# ㉿Nonrespiratory Illness

    ; occasionally manifest illness involving the skin, CNS, blood, heart, G-I tr. & joint

    1) skin lesion

       - exanthems

                   / *maculopapular rash, erythema multiforme, Stevens-Johnson synd

    2) CNS symptom

           - *meningoencephalitis, transverse myelitis, aseptic meningitis, cerebella ataxia, Guillain-Barre syndrome

       - encephalitis

                   / maybe occur without respiratory symptoms

               / *seizure (50%), impaired consciousness (75%), meningeal signs (85%)

                   / *CSF : normal

    3) hematologic symptom

           - hemolysis with positive coombs test, thrombocytopenia, coagulation defects

    4) GI symptom

           - mild hepatitis, pancreatitis, protein-losing hypertrophic gastropathy

    5) CV symptom

           - myocarditis, pericarditis, rheumatic fever-like synd

           - arrhythmia

           - ST & T wave change, cardiac dilatation with heart failure

    6) MS symptoms

           - *transient monoarticular arthritis

Diagnosis

  1. definite diagnosis of mycoplasmal inf. early in the clinical course

     : no specific clinical, epidemiologic or lab. observation

  2. serum cold hemagglutinin titer 1:64↑

     positive IgM M. pneumoniae antibody

     → support the Dx

Treatment

  1. M. pneumoniae

   ① EM, clarithromycin, azithromycin

      : exceptionally sensitive in vitro

   ② cell wall이 없기 때문에 Pc에 resistant

  2. EM & TC

     : effective in shortening the course of mycoplasma illness

  3. EM

   ① the duration of choice in small children

      : 이 age group에서는 TC의 toxic effect때문에

   ② 보통 7-10일의 defervescence후 several day동안 full therapeutic dose를 주어야 한다.

  4. 8 yr.이후에서는 TC가 alternative choice

  5. clinical course를 개선시키는 이들 약제의 efficacy에 불구하고 organism을 eradicate시키지는 못함.

Genital Mycoplasmas

* Mycoplasma hominis & Ureaplasma urealyticum

   1. human urogenital pathogen

   2. associated with sexually transmitted disease (STDs)

      such as nongonococcal urethritis or puerperal infections such as endometritis

Etiology

    : M. hominis & U. urealyticum

Clinical manifestation

 1. U. urealyticum

  ① clinically inapparant chorioamnionitis

     : eightfold increase in fetal death or premature delivery

  ② an important role in the development of bronchopulmonary dysplasia or

     chronic lung ds.(CLD) of premature infants born with RDS

 2. U. urealyticum meningitis

    : associated with intraventricular hemorrhage & hydrocephalus

    meningitis due to M. homonis

    : benign

 3. neonatal conjunctivitis, lymphadenitis, pharyngitis, pneumonitis, osteomyelitis, scalp abscess

 4. old children & adolescents

    : genital mycoplasma

      → associated with STDs & uncommon focal infections outside the genital tract

  5. U. urealyticum

   ① confirmed pathogen of nongonococcal urethritis

   ② male의 case 30%에서 이 organism단독 혹은 Chlamydia trachomatis와 동반해서 야기됨

  6. female

   ① rarely urethritis

   ② despite the high vaginal colonization rates

      → vaginitis or cervicitis: uncommon

Diagnosis

 1. isolated from urine, blood, CSF, tracheal aspirates, pleural fluid , abscess, lung tissue

 2. genital tract inf.의 진단은 difficult

    : high colonization rates in the vagina & urethra

 3. nongonococcal urethritis

    : confirmed by Gram stain of urethral discharge showing

      at least 3 polymorphonuclear leukocytes/oil-immersion field, & absence of Gram-negative diplococci

 4. urethral swab or exudate

    : cultured for C. trachomatis & U. urealyticum

Treatment

 1. symptomatic CNS inf.

    : Doxycycline recommended

 2. EM, theophylline을 동시에 투여받는 환자에서 사용시

    : serum theophylline level을 monitor

      → antibiotics가 theophylline metabolism을 inhibition 하기 때문

 3. nongonococcal urethritis

    : TC, doxycline, EM으로 orally로  7일간 Tx.

 4. U. urealyticum strain의 10-40%정도가 TC-resistant

    : TC tx.실패시 EM이 durg of choice

Chapter 197. Chlamydia

 

* Chlamydiae

   : obligate intracellular bacteria, DNA & RNA가짐

* the four recognized species

 1. Chlamydia trachomatis, C. pneumonia (TWAR), C. psittaci, & C. pecorum

 2. C. trachomatis : subdivided

                   . lymphogranuloma venereum (LVG)

                   . trachoma

* developed countries에서

   C. trachomatis

      : the most prevalent sexually transmitted ds.

        1. urethritis in men

        2. cervicitis & salphingitis in women

        3. conjunctivitis & pneumonia in infants

* C. pneumoniae

     : increasingly recognized as a common cause of respiratory disease

       - including bronchitis & pneumonia in both children & adults

* C. psittaci & C. pecorum

     : primary animal pathogens

INFECTIONS CAUSED BY CHLAMYDIA TRACHOMATIS

Trahoma

 1. trachoma

  ① the most important preventable cause of blindness in the world

  ② starts as a follicular conjunctivitis, usually in early childhood

  ③ follicle heal → conjunctival scarring → entropion & trachiasis

  ④ constant trauma에 의해 corneal ulceration → scarring & blindness

 2. Dx.: WHO에서는 four criteria중 2개이상 일때

  ① lymphoid follicle on the upper tarsal conjunctivae

  ② typical conjunctival scarring

  ③ vascular panus

  ④ limbal follicles

 3. ds.의 active stage동안 culture혹은 staining methods에 의해 Dx. confirm

Oculogenital infections in adults & adolescent

Epidemiology

  1. men에서 nongonococcal urethritis의 모든 case원인의 30-50%이다.

  2. gonorrhea갖고 있는 men의 50%에서 C. trachomatis coinfection

  3. women에서 genital chlamydial inf의 Cx은

     perihepatitis (Fitz-Hugh-Curtis synd.)과 salpingitis

     : salpingitis는 significant morbidity야기

         infertility와 ectopic pregnancy

Diagnosis

# definitive diagnosis of genital Chlamydial inf.

    ; *isolation of the organism in tissue culture from the urethra in men & the endocervix in women

Treatment

  1. The 1993 STD treatment guidelines from the Centers for Disease Control (CDC)

   ① doxycycline 100mg bid for 7 days

      azithromycin 1g single dose

   ② Tx. of uncomplicated genital infection in men & nonpregnant women

      : pregnant women에는 사용 안됨

  2. alternative regimen

     : ofloxacin 300mg bid for 7 days

       → cannot use during pregnancy or in person ≤ 17 yr of age

  3. pregnant women에서

     CDC recommended three different regimens

     : oral EM base or ethylsuccinate (800mg qid for 7 days or 400mg qid for 14 days)

       or amoxicillin 500mg tid for 7-10 days

Perinatally transmitted infections

# cervical Chlamydial infection of pregnant women

  ; 20-30%

# risk of transmission from mother to infant

  ; about 50%

# infection sites

    ; *conjunctivae, nasopharynx, rectum, vagina

    ; *70% nasopharynx

Inclusion Conjunctivitis

  1. Chlamydial-positive mother에서 태어난 infants 30-50%

     : develop conjunctivitis

  2. presentation: variable

     mild conjunctival injection with scant mucoid discharge에서

      severe conjunctivitis with copious purulent discharge, chemosis, & psuedomembrane formation까지

Pneumonia

  1. onset

   ① 1-3mo. age, incidious

   ② persistent cough, tachypnea, lack of fever

  2. auscultation

   ① rales

   ② wheezing (uncommon)

  3. distinctive lab. finding

   : presence of peripheral eosinophilia (>400 cells per mm³)

  4. the most consistent finding on chest radiography

   : hyperinflation accompanied by interstitial or alveolar infiltrates

Infection At Other Sites

    ; perinatally acquired rectal, vaginal, nasopharyngeal infections

           - *persist for at least 3yr

Diagnosis of C. Trachomatis Conjunctivitis & Pneumonia

  1. the gold standard

     : isolation by culture of C. trachomatis from the conjunctiva or nasopharynx

  2. noncultural methods

     : diagnosis of Chlamydial conjunctivitis

       DFA & EIA → 이들 test는 culture와 비교했을때 sensitive test는 ≥ 90%,

                       specificities는 ≥ 95%를 보여준다.

Prevention & Treatment

  1. Tx. of C. trachomatis inf

     : 1-2 wk of EM

  2. The CDC & the American Association of Pediatrics (AAP)

     : oral EM suspension, 50mg/kg/24hr in 2 or 4 divided doses. for 10-14 days

       → for both conjunctivitis & pn in infants

  3. the failure rate with oral EM: 10-20%

Infection In Older Children

Lymphogranuloma venereum

   * LGV: a systemic, sexually transmitted disease

Clinical Manifestation

  1. the first stage of LGV

     : appearance of the primary lesion, a painless, transient papule on the genitals

  2. the second stage

     : lymphadenitis of lymphadenopathy with enlarging, painful buboes, usually in the groin

  3. the tertiary stage

     : full-blown genitoanorectal syndrome with rectovaginal fistula, rectal stricture &

       urethral destruction

Differential Diagnosis

    LGV: diagnosed by culture of C. trachomatis from a bubo aspirate or serologically

Treatment

  1. Doxycycline, 100mg by mouth for 21 days

     : recommended treatment

  2. alternative regimens

     : EM 500mg qid for 21 days

       sulfisoxizole 500mg qid for 21 days

INFECTIONS DUE TO C. PNEUMONIAE, STRAIN TWAR

Epidemiology

  * C. pneumoniae

    : 10-20% of community-acquired "atypical" pn.

      (including acute chest syndrome in children with sickle-cell ds)

    : 10% of bronchitis

    : 5-10% of pharyngitis

Clinical manifestations

 * Pn

  1. classic atypical (or nonbacterial) pn.

  2. fever, malaise, headache, cough, pharyngitis

Diagnosis

  1. specific diagnosis of C. pneumoniae inf

     : based on isolation of the organism in tissue culture & serology

  2. criteria for serologic diagnosis of C. pneumoniae inf

   ① acute infection

     : fourfold rise in the MIF IgG titer

       or single IgM titer ≥ 1:16 or a single IgG titer ≥ 1:512

   ② past or pre-existing infection

     : IgG titer ≥ 1:16 & < 1:512

   ③ these criteria: based mainly on data from adults

Treatment

  1. C. psittaci, C. pneumoniae와 같이

     : highly resistant to sulfonamides

  2. optimum dose & duration of therapy

     : uncertain

  3. preliminary date in children with C. pneumoniae

     : EM suspension of 40-50mg/kg/24hr day for 10-14 days

       → effective in eradication of the organism from the nasopharynx in more than 80% of  cases

INFECTIONS DUE TO C. PSITTACI (PSITTACOSIS)

Clinical Manifestation

    ; usually abrupt

  ; *fever, cough & headache

           - high fever, nonproductive coughing

           - severe headache considered meningitis

    ; chest X-ray

           - abnormal with variable infiltrates

           - pleural effusion

    ; abnormal LFT

Diagnosis & Treatment

    ; Hx. of exposure to birds

        - very important

    - psittacosis가진 환자의 20%에서 알려진 contact(-)

    ; ★Classified Based On Lab. Findings Or Exposures

       ① confirmed case

           : clinical specimen yielding C. psittaci

                        or compatible clinical illness & fourfold rise in CF antibody titer

       ② presumptive case

           : compatible clinical illness & single serum sample titer of ≥ 1:32

                           or a stable antibody titer of ≥ 1:32 in two samples

       ③ suspect case

           : a case that dose not meet the criteria in one or two but is associated with another case of avian chlamydiosis

    ; recommended treatment for psittacosis in humans

       - 500mg TC every 6hr, orally for 7-10 days

    - EM 2g day for 7-10 days - alternative regimen

Chapter 198. Lyme Disease (Lyme Borreliosis)

; *▲common vector-borne disease in US

Etiology

    ; *spirochete Borrelia burgdorferi

Epidemiology

# transmission

    ; bite of an infected tick

           - Ixodes species in US

Clinical manifestations

Early Localized Disease

    ; *typical annular rash called “erythema migrans”

           - first clinical symptoms

           - usually occurs 7-14days after bite

           - anywhere on the body

            / ★▲common locations

                        : *axilla, the periumbilical area, the thigh, the groin

Early Disseminated Disease

   ① common manifestation

     : caused by hematogenous spread of the organisms to multiple skin sites

   ② aseptic meningitis

   ③ rarely, carditis with varying degrees of heart block

   ④ cranioneuropathies

   ⑤ paralysis of the facial (seventh) nerve

Late Disease

    ; *arthritis

       - beginning months after the initial infection

           - large joint involvement, esp. knee (90%)

Congenital Lyme Ds

     : extremely rare

Diagnosis

# clinical manifestation

    ; not specific

# isolation of B. burgdorferi

    ; ★diagnostic

    ; *unuseful due to expensive medium, long culture periods(4wks), low sensitivity

# identification of B. burgdorferi

    ; silver stains(Warthin-Starry or modified Dieterle), immuno-histochemical strains(with monoclonal or polyclonal Ab) in biopsy

    ; unuseful due to false positive & low sensitivity

# ★Demonstration Of Ab To B. Burgdorferi

    ; usually confirmation diagnosis

    ; *specific IgM 3-4wks after infection

    ; *specific IgG 6-8wks after infection

           - peak after 4-6mo

           - remain elevated indefinitely

    1) immunofluorescent antibody test

    2) enzyme-linked immunosorbent assays (ELISA)

           ; 1) 보다 더 선호

           ; false positive

                   - cross-reaction with other spirochetal infection

                   - certain viral infection

                   - autoimmune disease

    3) immunoblots

           ; *more sensitive & specific than ELISA

           ; not estabilised minimum criteria for “positive”

# *결국 의심되는 임상 질환을 가진 환자에게서 serologic test을 실시함으로써 specificity을 높이는 수 밖에는 없다.

Prevention

  1. endemic area에서는 children이 종종 deer ticks에 의해 물릴수 있는데 Lyme ds.가

     발생되는 risk는 low (1-2%)

  2. more resonable approach to preventing Lyme ds.

   ① wear appropriate protective clothing when entering tick-infested areas

   ② check for & remove ticks after spending time in such areas

Treatment

★Table 198-1

Prognosis

    : excellent - for children

Chapter 199. Tuberculosis

# 감소 추세에 있다가 지난 10 년간 drametically increased

Etiology

; M. tuberculosis, M. bovis, M. Africanum - order Actinomycetales and family Mycobacteriaceae.

; grow best at 37-41℃

; produce niacin, lack pigmentation

; * Hallmark of all mycobacteria

    - acid-fastness(capacity to form stable mycolate complexes with arylmethane dyes such as crystal violet, carbolfuchsin, auramin, rhodamine)

    - resist decoloration with ethanol, hydrochloric acids

; slowly growth

    - generation time 12-24 hr

; isolation

    - solid synthetic media에서 3-6 wk, drug sensitivity 4 wk

    - selective liquid medium(BACTEC radiometric system)에서 1-3 wk, drug sensitivity 3-5days

; *Characteristics of M. tuberculosis

    - colony morphology

    - produce niacin but no pigment

    - reduce nitrate

    - produce catalase

; ★PCR

    - sensitivity가 culture와 비슷

    - within hours

Epidermiology

Infection And Disease

; 인구의 약 1/3 인 20억이 M. tuberculosis에infected.

; southeast asia, india, china, africa, latine america에 common.

; prevalent 증가 : poor nutrition, overcrowding, inadequate health care, displacement.

; adult : 2/3 male, children : slightly female predorminant

; white: older age에 많다.

; non-white

    - ▲ in young adults & children less than 5yr

; *5-14yrs - " favored age "

; drug resistant tuberculosis의 증가

  - 14 %에서 최소한 한가지 약제에 resistant

  - 3 %에서 INH, RIF에 resistant

  - some countries에서 20-50 % 정도 resistant rate가 보고됨.

  - major reasons : poor patients adherance to Tx, inadequate drug regimens.

Transmission

; *person to person - mucus droplet nuclei, airborne.

    - rarely by direct contact

♥Transmission Chance의 증가

    ; sputum의 Acid Fast smear (+)

    ; extensive upper lobe infilteration or cavity

    ; copious thin sputum production

    ; severe and forceful coughing      

; in most adults, chemotherapy 시작 2 wk후부터 no transmission

    - some patients remain for many weeks

; ♥young children - rarely infect other children, adult

    - ♥why ?

           / sparse bacilli in endobroncheal secretion

           / absent cough

           / lacks of tussive force required to suspend infectious particles of correct size

Pathogenesis and Immunity

# primary complex

    ; local infection at the portal of entry( 98%이상) & regional L/N

# bacilli의 대부분은 killed, 그러나 nonactivated marcrophage 내의 일부는 lymphatic vessel을 따라 regional L/N 로 carry.

    ; lung에 primary infection이 있다면 hilar L/N가 involve되고 focus가 upper lobe일때 paratracheal node로 drained된다.

  ; lung parenchyma, L/N는 2-12wk후 tissue hypersensitivity가 developed된다.

# primary focus의 parenchmal portion

    ; caseous necrosis, encapsulation

           --> calcification, fibrosis

           --> complete healing

    ; sometimes focal pneumonitis, pleuritis

# L/N lesion

    ; *parenchymal lesion보다 less complete healing

    ; persist viable M. tuberculosis for decades

    ; attach bronchial wall

           --> endobronchial tuberculosis

    ; cesium

           --> complete obstruction of bronchus

           --> *collapse-consolidation or segmental lesion

# Disseminated Tuberculosis

    ; primary complex에서 blood, lymphatic vessel을 통해

    ; circulatory bacilli의 수가 많거나 host response가 inadequate할때 발생.

    ; *often early manifestation within 2-6month of infection

# clinically significant lymph node or endobroncheal Tb

    ; 3-9 month내에 발생.

# bone, joint Tb : 몇년후

# renal Tb : 10년이상.

# reactivation Tbc

    ; endogenous regrowth of bacilli persisting in partially encapsulated lesion

    ; *more than 1yr after primary infection

    ; *children에서는 rare.

    ; *▲common lesion

           - *apex of upper lobe

           - due to great oxygen tension, blood flow

# M. Tuberculosis infection후 disease 발현

  ; immunocompetent adult : 5-10 %

  ; infants : 40 %에서 1-2년내에 발생, children시기에 감소.

# extrapulmonary manifestation

    ; immunocompetent adult - 10 %내외

    ; children에서는 25-35 %

Pregnancy And Newborn

; congenital Tb. : rare

    - due to infertility of female genital Tbc

; congenital transmission

    - *transplacental transmission from placental lesion to umbilical vein

           / *▲common

         / more common in primary infection than reactivation

    - aspiration or ingestion of infected amniotic fluid

; ★Fetal Tuberculosis

    - ★first reach fetal liver : primaty focus with periportal LN

           -->         hematogenous spread

           --> many organ

; ★neonatal tuberculosis

    - *postnatal airborn transmission from adult

           / *▲common route

Immunity

; Ab - play little role

# After infection

    ; *short period of uninhibited growth in both alveolar space & macrophge

           - sulfatides in mycobacteria inhibit fusion of macrophage phagosome & lysosome

    ; ★Cell Mediated Immunity

           - *4-8wk에 developed, 동시에 tissue hypersensitivity가시작.

           --> secretion of lymphokines and other mediators

           --> attract other lymphocytes & macrophages

           --> high concentration of lytic enzyme

           --> mycobactericidal effect

           --> prevention of initial infection progression

# ★Pathologic Event

    ; depend on mycobacterial antigen load & tissue hypersensitivity

    ; antigen load가 작고 tissue sensitivity가 높으면

           / lymphocyte, macrophage, fibroblast의 organization

                   --> granulation formation

    ; antigen load & tissue sensitivity가 높으면

           / granulation formation이 less organized

                   --> incompletet issue necrosis --> caseous material formation.

    ; tissue sensitivity가 낮다면(infant, immunocompromized pt)

           / infection은 diffuse, dissemination, local tissue destruction.

# Tissue necrosis factor, cytokines

    ; cellular destruction, tissue damage의 promoting.

# ★Tb 자체가 host immune response를 suppress한다.

Tuberculin skin test

; PPD 0.1 ml (5 TU) intradermal injection.

    - 48-72hr  indulation의 amount로 response 결정

    - *때때로 72hr이 지나서 induration관촬

           / positive result.

㉿False Negative

    ; *poor technique or misreading results - ▲

    ; very young age

    ; malnutrition

  ; immunosuppression (by disease or drug )

  ; viral infection (measles, mumps, varicella, influenza)

    ; live-virus vaccines.

    ; overwhelming tuberculosis

  ; corticosteroid therapy - variable

           - corticosteroid therapy시작시 tuberculin test는 reliable하다.

; Tb를 가진 *immunocompetent pt의 10%, meningitis, disseminated ds를 가진 pt의 50%에서 초기에 PPD에 반응이 없다.

  - antituberculosis therapy 몇 달 후에 reactive.

㉿False Positive Reaction

    ; cross sensitization to Ag of NTM

        - cross reaction은 몇달-몇년동안 transient하고 indulation은 10-12mm이하.

    ; previous BCG(bacille Calmette-Guerin) vaccination

           - 1/2 of infants reactive tuberculin skin test (+)

       - 처음 positive skin test후 2-3yr에 reactivity (-)

       - old children, adult에서 BCG vaccination more tuberculin reactivity

                   / vaccination후 5-10년에 reactivity(-)

                 / indulation이 10mm이하

; Tb에 대한 risk가 없는 children에서 small skin test reaction

    - false positive result.

㉿ Strong Positive Reaction

    ; bone, joint Tbc

    ; DM

    ; erythma nodosum

    ; phlyctenular conjunctivitis

# ★High risk of infection

    a. 최근 infectious person과 contact

    b. clinical illness가 Tb로 생각될때

    c. HIV infection

    d. immunosuppression시.

    --> *5mm이상시 positive result

* 3세 이하의 children과 다른 high risk group에서 10mm이상시 positive로 생각.

* low risk person (특히 prevalance가 낮은지역)은 positive reaction은 15mm이상

# 1-TU and 250-TU

    a. 1-TU : pt가 5-TU에 severe reaction을 보일때 사용

    b. 250-TU : 5-TU에 대한 interpretation이 controversal할때 사용

            250-TU에 반응이 없다면 Tb가 아니다.

          ---> 일반적으로 잘 사용안함

Clinical Manifestations

Primary Pulmonary Disease

; primary pulmonary complex : parenchmal focus + regional L/N.

; 약 70 %에서 subpleural, localized pleurisy.

; initial lesion

    - usually not visible in chest X-ray

    - maybe localized, nonspecific infilteration

; initial infection의 risk는 all bolar sigment가 equal

; case의 25 %에서 2개이상의 primary foci를 가진다.

; * Hallmark

    - initial lung focus의 relatively small size에 비해 relatively large size의 regional lymphadenitis.

; 대부분의 case에서 parenchymal infilterate와 adenitis는 early resolve되지만 hilar L/N는 특히 infant에서 계속 enlarge된다.

; ★Common Sequence

    - hilar adenopathy --> focal hyperinfilteration --> atelectasis

    - collapse-consolidation or segmental tuberculosis

; forign body aspiration 과 X-ray finding이 비슷.

Clinical Manifestation

; nonproductive cough, mild dyspnea▲

; fever, night sweat, anorexia, decreased activity, wt. gain failure, true failure to thrive syndrome

; pulmonary sign은 less common.

; broncheal obstruction --> wheezing, BS감소 with tarchypnea, respiratory distress

; children

    - *lobar pneumonia without impressive hilar adenopathy을 보일 수도 있다.

; primary infection이 계속적으로 destructive, liquefaction of the lung parenchyma

    --> thin walled primary tuberculosis cavity를 형성.

    --> rarely bullous tuberculosis

    --> pneumothorax by rupture

Diagnosis

; confirmation by isolation of M. tuberculosis

    - *early morning gastric content

    - 3번 연속으로 aspiration하여 organism을 찾을 확율은 50 % 이하일 수 있다.

; positive skin test, abnormal x-ray finding, consistent with Tbc

    - Tb 진단가능

Progressive Primary Pulmonary Disease

; rare하지만 primary focus가 enlarged되고 large caseous center로 developed되면 serious complication을 가진다.

; liquefaction --> necrotic debris가 adjuscent bronchus --> intrapulmonary dissemination.

; sign & Sx.

    - high fever, severe cough with sputum production, wt. loss, night sweat, diminished BS, rales, dullness, egophony

; 적절한 치료시 slow recovery is excellent.

Reactivation Tuberculosis.

; childhood에 rare, aldolescence에서 occur.

; 2세이전에 healed Tbc의 경우는 chronic reactivation pul. disease rare but 7세이후의 경우는 more common

; *extensive infilterates or thick walled cavities in the upper lobes.

    - ▲ X-ray finding

; fever, anorexia, malase, wt. loss, night sweat, productive cough, chest pain등이primary pulmonary Tb보다 더 잘나타남.

; 대부분의 Sx. sign은 적절한 치료 수 주내에 improved되고 cough가 몇달간 지속될수 있다.

Pleural Effusion

; *asymptomatic local pleural effusion

    - primary Tb에 frequent

large and clinically significant effusion : primary infection 몇달-몇년후

; 6세이하에서는 infrequent, 2세이하에서는 rare.

; 일반적으로 unilateral 이지만 bilateral도 올 수 있다.

; radiographic abnormality가 physical finding이나 Sx. 보다 더 잘 나타난다.

; clinical onset은 sudden하고 low to high fever, shortness of breath, deep respiration시의  chest pain, diminished breath sound가 특징적임

; skin test : 70-80 %에서 positive

; prognosis는 excellent하고 radiographic resolution은 몇달 걸림.

★ Pleural Fluid

    ; yellow, 때때로 tinged blood

    ; S.G : 1.012 -1.025

    ; protein : 2-4 g/dl

  ; glucose : low 20 - 40 mg/dl

  ; WBC

           - several hundred to thousand

           - early PMN prdorminance

    ; *AFB stain - almost never positve

    ; *culture : 30 - 70 % (+)

; *pleural membrane biopsy

    - more dignositic use

Pericardial Disease

; 0.5 - 4 % rare

; *▲common cardiac Tbc

; direct invasion or lymphatic drainage

; presenting Sx.

    - N-S ( low grade fever, malaise, wt. loss, chest pain )

    - pericardial friction rub

    - pulsus paradoxus를 가진 distant heart sound

; pericardial fluid

    - serofibrinous or hemorrhagic.

    - AFB stain : 보통 negative

    - culture : 30 - 70 % (+)

; *pericardial Bx

    - *more reliable culture yields

Lymphohematogeneous ( Disseminated ) Disease

; liver, spreen, skin, lung apex로 disseminated

; lymphohematogeneous dissemination에 의한 clinical picture는 primary focus로부터 released 되는 organism의 수와 host immune response의 adequacy에의해 결정.

Clinical Manifestation

; usually asymptomatic

; spiking fever

; *multiple organ involvement 가 common

    - hepatomegaly, spleenomegaly, lymphadenitis.

  - skin에 papulonecrotic tuberculids

  - bone, joint, kidney도 involve.

  - meningitis : late에 생김.

; *Miliary disease

    - *▲clinically significant form of disseminated Tb.

    - massive tubercle bacilli into bloodstream

        --> disease in two or more organs

    - *occurs within 2-6mo of initial infection

    - *▲common in infant, young children, malnourished or immunosuppressed patients

; onset

    - incidious, sometimes explosive

    - anorexia, wt. loss, low-grade fever

    - absent abnormal physical finding

; *generalized lymphoadenopathy & hepatosplenomegaly

    - 수 주이내 약 50 %에서 발생

; normal chest X-ray, minor or abscent respiratory Sx

  - but higher fever

; 몇주 더 지나면 tubercle infiltration --> dyspnea, cough, rales, wheezing

    --> *alveolar-airblock syndrome

    --> frank respiratory distress, hypoxia, pneumothorax, pneumomediastinum.

; 20 - 40 % 에서 meningitis, peritonitis의 Sx. sign (+)

; choroid tubercles : 13 - 87 % 에서 occur.

; Tuberculin test : 40 %이상에서 nonreactive.

Diagnosis

; early sputum or gastric aspirate culture : low sensitivity

; *liver, BM biopsy - more yields

; infectious tuberculosis를 가진 adult와의 최근에 exposure 된 history가 가장 중요.

Prognosis

; slow resolution

; *fever declines within 2-3wk of chemotherapy

; chest x-ray

    - *not resolution for many months

; excellent prognosis if early adequate treatment

Upper Respiratory Tract Disease

laryngeal Tb : coupy cough, sore throat, hoarseness, dysphagia

             -- 대부분 extensive upper lobe disease

middle ear Tb : hematogeneous or infected pul. secretion이 middle ear.

              : painless otorrhea, tinnitis, decreased hearing, facial paralysis,

                perforated tympanic membrane ---> 진단이 힘듬.

 

Lymph Node Disease(=scrofula)

; *extrapulmonary Tb의 most common form

; 대부분 initial infection  6-9 month에 생김.

; tonsillar, ant. cervical, submandibular, supraclavicular node

  - firm, not hard, discrete, nontender, often feel fixed to underlying or overlying tissue.

; 대부분 unilateral, but bilateral도 가능.

; low grade fever외에 다른 Sx. sign은 없다.

; tuberculin skin test usually reactive.

; onset

    - acutely enlargement of L/N, high fever, tenderness

  - if untreared, progresses to caseation necrosis.

; Tb lymphadenitis는 antituberculosis therapy에 반응이 좋다.

; *surgical remove는 not adequate therapy

  - because a part of systemic infection

; Dx. : excisional Bx.

; DDx. : NTM, cat-scratch ds, tularemia, brucellosis, toxoplasosis, tumor, brancheal cleft cyst, cystic hygroma

Central Nervous System Disease

; primary infection의 lymphohematogenus dissemination시에 cerebral cortex나 menings에

 metastatic caseous lesion의 형성에 의해 생김.

# Pathogenesis

    - bacilli into subarachnoid space

    - gelatinous exudate

    - infiltrate corticomeningeal blood vessels

    --> inflammation, obstruction, infarction of cerebral cortex

; brain stem involve

    - CN III, VI, VII dysfunction

; communiting hydrocephalus.

; *0.3 % of untreated primary infection.

; *most common age - 6 mo-4 yrs

★ Three Stage

lst stage : 1 - 2 wk

    - nonspecific Sx. : fever, headache, irritability, drawsness, malaise

  - focal neurologic sign (-)

  - infant : stagenation or loss of developmental milestones.

2nd stage : more abruptly (hydrocephalus or IICP 때문에)

    - common feature : lethalgy, nuchal rigidity, seizure, Kernig, Brudzinski sign(+), hypertonia, vomiting, CN palsy, other focal neurologic sign

    - meningeal irritation sign없이 encephalitis의 sign

           / disorientation, movement disorders, speech impairment

3rd stage

    - coma, hemiplegia, paraplegia, hypertension, decerebrate posturing, deterioration of vital sign, death

Diagnosis

; Tuberculin skin test : 50 % nonreactive.

; Chest x-ray : 20 - 50 %에서 normal

★ CSF finding

    - WBC : 100 - 500 cells/mm3

    - PMN이 initially present --> lymphocyte predorminant

    - Glucose : 40 mg/dl이하 (rarely <20 mg/dl)

    - protein : elevated

           / marked high 400 - 5000 mg/dl secondary hydrocephalus, spinal block

; *AFB culture의 성공 여부는 CSF의 양과 관계가 있다.

  - *5-10 ml의 lumbar CSF를 obtained했을때 AFB stain positive는 30 % 이고, culture positive는 50 - 70 % 이다.

; CT, MRI : 초기에  normal

  - 진행이 됨에 따라 basilar enhancement, communicating hydrocephalus, cerebral edema, early focal ischemia등이 나타남.

# Tuberculoma

    - 임상적으로 brain tumor와 비슷, 대부분 singular

  - *adult : supratentorial, children : infratentorial (cerebellum 주위)

    - surgical excision

           / for DDx from brain tumor

    - 대부분 medical management에 의해 resolve.

    - ring-like lesion, avascular in CT

    - paradoxical development

           / effective chemotherapy를 받고 있는 환자에서 발생

           / not represent failure of drug treatment

Bone & Joint disease

; *vertebrae ▲

; tuberculous spondylitis의 classic manifestation은 Pott disease로 진행

  --> vertebral body의 destruction --> gibbus deformity와 Kyphosis

; Tb의 late complication.

Abdominal & Gasterointestinal Disease

; oral cavity, pharynx

    - rare

    - painless ulcer on the mucosa, plate, tonsil with enlargement of the regional L/N

; 대부분 extensive pulmonary lesion이 있으나 없는 경우에도 올 수 있다

TBC peritonitis

; *young man ▲

    - *aldolescence에서 uncommon

  - children에서 rare

; rarely L./N , omentum, peritonium이 mattered되고 " doughy " irregular nontender mass.

; ascitis, low grade fever 가 common.

; MT usually reactive

; Dx

    - *paracentesis with stains, culture

Tbc enteritis

; hematogeneous dissemination or swallowing of tubercle bacilli

; *jejunum, ileum near Payer's patches, appendix

    - *▲ site

    - shallow ulcer

    - pain, diarrhea, constipation, wt. loss with low grade fever.

; chronic GI complants가 있고 reactive tuberculosis skin test가 있는경우 꼭 suspected해야

; Dx

    - Bx. AFB & culture

Genitourinary disease

Renal Tbc

; rare in children <--- incubation period가 several yrs이기 때문에

; in true renal Tb에서 small caseous foci --> renal parenchymal disease

  --> M.tubeculosis를 tubules로 release --> cortex 주위의 large mass

 --> renal pelvis 로 fitula를 통해 bacteria discharges

--> ureter, prostate, epididermis로 spread

Sx. ; 초기에 clinically silent --> dysuria, flank, abdominal pain, gross hematuria

     다른 bacteria에 의한 superinfection이 있으면 more acute Sx. 이 있다.

Cx. : hydronephrosis, ureteral stricture

Dx. : urine culture : 80 - 90 % positive

AFB 50 - 70 % positive : large volume of urine sediment

skin test : 20 % 이상에서 non-reactive

IVP : mass lesion, dilatation of the pro. ureter, multiple small filling defect, ureteral stricture가 있다면 hydronephrosis가 발생.

* 대부분 unilateral

Genital tract Tbc

; puberty 전에는 uncommon

; 보통 lymphohematogenous spread이나 intestinal tract이나 bone에서 direct spread도 가능.

 aldolescent girl : primary infection시 genital Tb 가능

 fallopian tube : 90 - 100 % , endometrium 50 %, ovary 25 %, cervix 5 %

 Sx. : low abdominal pain, dysmenorrhea, amenorrhea,

      systemic manifestation은 보통 abscent

 X-ray : normal

 skin test : usually reactive.

Disease In HIV-Infected Children

; skin test reactivity : abscent

    - 진단에 missed 가능성

; culture confirmation이 difficulty

; HIV-infected children에서 Tb는 more severe하고 disseminated.

; most common Sx

    - pulmonary Sx. with fever, wt. loss.

Perinatal Disease

; Sx. & sign이 태어날 때도 있을 수 있지만 *more commonly 2 - 3 wk에 나타남.

; Sx. & sign

   - respiratory distress, fever, hepatic,splenic megaly, poor feeding, lethalgy, irritability, lymphadenopathy, abdominal distension, failure to thrive, ear drainage, skin lesion.

; chest x-ray

    - *miliary pattern most often.

; Hilar, mediastinal lymphadenopathy, lung infilterate : common

; generalized lymphadenopathy, meningitis : 30 - 50 % (+)

Diagnosis

; *maternal or family Hx - ▲important clue

; infant's tuberculin skin test

    - initially negative --> 1 - 3 month 후에 positive.

; early morning gastric aspirates

; middle ear discharge, BM, tracheal aspirates, biopsy tissue

    - direct AFB stain

    - useful, performed

; CSF Ex.과 culture는 균의 isolation이 낮지만 꼭 시행해야 한다.

; congenital Tb의 진단이 del